dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e9f16d4033b3426ca548f02ccc0c2b35
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.Cc1ccc(NS(N)(=O)=O)nc1>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C)cn1
CC=1C=CC(=NC1)NS(=O)(=O)N.ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1>>ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=C(C=C1)C)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:22]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][cH:19][cH:20]2)[n:21]1.[NH2:23][S:24](=[O:25])(=[O:26])[NH:27][c:28]1[cH:29][cH:30][c:31]([CH3:32])[cH:33][n:34]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([Cl:12])[...
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.Cc1ccc(NS(N)(=O)=O)nc1
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C)cn1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(Nc1ccccn1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9].[#7:10]-[#16:11](-[NH2;D1;+0:12])(=[O;D1;H0:13])=[O;D1;H0:14]>>[#7:10]-[#16:11](=[O;D1;H0:13])(=[O;D1;H0:14])-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9]
17
[{"value": 17.0, "product": "ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=C(C=C1)C)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the procedure described in referential Example 1e), 5-methyl-pyridine-2-sulfamic acid amide (252 mg, Referential Example 20) was reacted with 4,6-dichloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (410 mg, Referential Example 1d)) to give 5-methyl-pyridine-2-sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccncc1.c1ccncc1
HCl
null
null
null
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.Cc1ccc(NS(N)(=O)=O)nc1>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C)cn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3a2f19201fb4458e938ba790074c31b8
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.NS(=O)(=O)Nc1ccccn1>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
N1=C(C=CC=C1)NS(=O)(=O)N.ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1>>ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:22]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][cH:19][cH:20]2)[n:21]1.[NH2:23][S:24](=[O:25])(=[O:26])[NH:27][c:28]1[cH:29][cH:30][cH:31][cH:32][n:33]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([Cl:12])[n:13][c:1...
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.NS(=O)(=O)Nc1ccccn1
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(Nc1ccccn1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9].[#7:10]-[#16:11](-[NH2;D1;+0:12])(=[O;D1;H0:13])=[O;D1;H0:14]>>[#7:10]-[#16:11](=[O;D1;H0:13])(=[O;D1;H0:14])-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9]
71.8
[{"value": 71.8, "product": "ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the procedure described in referential Example 1e), pyridine-2-sulfamic acid amide (60 mg, Referential Example 21) was reacted with 4,6-dichloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (100 mg, Referential Example 1d)) to give pyridine-2-sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-py...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccncc1.c1ccncc1
HCl
null
null
null
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.NS(=O)(=O)Nc1ccccn1>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9ec8837a87b248b2b9999eaadda6b40a
CCNS(N)(=O)=O.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
C(C)NS(N)(=O)=O.ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1>>ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
[NH2:23][S:24](=[O:25])(=[O:26])[NH:33][CH2:29][CH3:30].Cl[c:32]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][cH:19][cH:20]2)[n:21]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][...
CCNS(N)(=O)=O.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
283ee355c481da0ae43e8a4ead3e293aa3222fc998e480675e520fef4ed3791e
6303949decfda2ee299bbf5557020af70d269ae23a015f9213b4396280149edd
O=S(=O)(Nc1ccccn1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[n;H0;D2;+0:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c;H0;D3;+0:8]:1-[#8:9]-[c:10].[CH3;D1;+0:11]-[CH2;D2;+0:12]-[NH;D2;+0:13]-[S;H0;D4;+0:14](-[NH2;D1;+0:15])(=[O;D1;H0:16])=[O;D1;H0:17]>>[Cl;D1;H0:7]-[c:6]1:[#7;a:5]:[c:3](-[c:4]):[n;H0;D2;+0:2]:[c:18](-[NH;D2;+0:15]-[S;H0;D4;+0:14](=[O;D1;H0...
100.5
[{"value": 100.5, "product": "ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=NC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the procedure described in referential Example 1e), ethyl-sulfamic acid amide (40 mg, Referential Example 22) was reacted with 4,6-dichloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (100 mg, Referential Example 1d)) to give pyridine-2-sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-4-pyrimid...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Sulfonamide.Aromatic halide.Ether
Sulfonamide.Sulfonamide.Ether
c1cncnc1
c1cncnc1.c1ccncc1
c1ccccc1.c1cncnc1.c1ccncc1.c1ccncc1
HCl
null
null
null
CCNS(N)(=O)=O.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl>>COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-74338b5aed30449facdcc0ace8215f09
Cc1ccc(-c2c(Cl)ncnc2Cl)cc1.Cc1ccc(NS(N)(=O)=O)cc1>>Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1
C(C)(C)N(CC)C(C)C.ClC1=NC=NC(=C1C1=CC=C(C=C1)C)Cl.[K].CC1=CC=C(C=C1)NS(N)(=O)=O>>ClC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C
Cl[c:11]1[n:12][cH:13][n:14][c:15]([Cl:16])[c:17]1-[c:18]1[cH:19][cH:20][c:21]([CH3:22])[cH:23][cH:24]1.[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][S:7](=[O:8])(=[O:9])[NH2:10])[cH:25][cH:26]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][S:7](=[O:8])(=[O:9])[NH:10][c:11]2[n:12][cH:13][n:14][c:15]([Cl:16])[c:17]2-[c:18]2[cH:19][cH:...
Cc1ccc(-c2c(Cl)ncnc2Cl)cc1.Cc1ccc(NS(N)(=O)=O)cc1
Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1
null
null
CO.CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(Nc1ccccc1)Nc1ncncc1-c1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[c:8].[#7:9]-[#16:10](-[NH2;D1;+0:11])(=[O;D1;H0:12])=[O;D1;H0:13]>>[#7:9]-[#16:10](=[O;D1;H0:12])(=[O;D1;H0:13])-[NH;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[c:8]
62.1
[{"value": 62.1, "product": "ClC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
48
HOUR
To 4,6-dichloro-5-p-tolyl-pyrimidine (Referential Example 7) (2.0 g) dissolved in DMSO (35 ml) was added di-isopropyl-ethyl-amine (1.46 ml) followed by addition of 4-methyl-phenyl sulfamic acid amide potassium salt (2.78 g) [prepared from the product described in Referential Example 19 and potassium tert.-butylate in m...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
CO.CS(=O)C
null
48
Cc1ccc(-c2c(Cl)ncnc2Cl)cc1.Cc1ccc(NS(N)(=O)=O)cc1>CO.CS(=O)C>Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-101c7ac50baf4d4999c44b012e398b23
Clc1ccc(-c2c(Cl)ncnc2Cl)cc1.NS(=O)(=O)NCc1ccccc1>>O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1
C(C)(C)N(CC)C(C)C.ClC1=NC=NC(=C1C1=CC=C(C=C1)Cl)Cl.[K].C(C1=CC=CC=C1)NS(N)(=O)=O>>ClC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)C1=CC=C(C=C1)Cl
Cl[c:13]1[n:14][cH:15][n:16][c:17]([Cl:18])[c:19]1-[c:20]1[cH:21][cH:22][c:23]([Cl:24])[cH:25][cH:26]1.[O:1]=[S:2](=[O:3])([NH:4][CH2:5][c:6]1[cH:7][cH:8][cH:9][cH:10][cH:11]1)[NH2:12]>>[O:1]=[S:2](=[O:3])([NH:4][CH2:5][c:6]1[cH:7][cH:8][cH:9][cH:10][cH:11]1)[NH:12][c:13]1[n:14][cH:15][n:16][c:17]([Cl:18])[c:19]1-[c:20...
Clc1ccc(-c2c(Cl)ncnc2Cl)cc1.NS(=O)(=O)NCc1ccccc1
O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1
null
null
CO.CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(NCc1ccccc1)Nc1ncncc1-c1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[c:8].[#7:9]-[#16:10](-[NH2;D1;+0:11])(=[O;D1;H0:12])=[O;D1;H0:13]>>[#7:9]-[#16:10](=[O;D1;H0:12])(=[O;D1;H0:13])-[NH;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[c:8]
44.1
[{"value": 44.1, "product": "ClC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)C1=CC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To 4,6-dichloro-5-(4-chloro-phenyl)-pyrimidine (Referential Example 9) (2.59 g) dissolved in DMSO (14 ml) was added di-isopropyl-ethyl-amine (1.8 ml) followed by the addition of benzyl sulfamic acid amide potassium salt (2.25 g) [prepared from the product described in Referential Example 22 and potassium tert.-butylate...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
CO.CS(=O)C
null
24
Clc1ccc(-c2c(Cl)ncnc2Cl)cc1.NS(=O)(=O)NCc1ccccc1>CO.CS(=O)C>O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3f15be0b70554171a09e916b132ee286
CO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1>>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OC
ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC.CO.C1CCOC1.[H-].[Na+]>>COC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC
[OH:36][CH3:37].Cl[c:35]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][c:17]2[cH:18][cH:19][c:20]([CH:21]([CH3:22])[CH3:23])[cH:24][cH:25]2)[n:26][c:27](-[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[n:34]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:...
CO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OC
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
320b907a829de2b489cb2f69345494f41d68001a72a3955182cde184381510f6
23dafde907f7a74dc1d4cc65967b00a9b318897fe61a3d3c4a9fddf320485f17
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[#7:7]):[c:8]:1-[#8:9].[C;D1;H3:10]-[OH;D1;+0:11]>>[#7:7]-[c:6]1:[#7;a:5]:[c:3](-[c:4]):[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:11]-[C;D1;H3:10]):[c:8]:1-[#8:9]
null
[]
80
CELSIUS
null
null
To a mixture of methanol (1 ml) and THF (2 ml) was added sodium hydride (100 mg, 60% dispersion in mineral oil) followed by the addition of 4-i-propyl-phenyl sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (100 mg, Referential Example 1e)). DMF (0.5 ml) was added and the reaction mixtur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Methanol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1ccncc1
HCl
CN(C)C=O
80
null
CO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1>CN(C)C=O>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a308b8d7315b46f3a3735372c111dddd
C=CCO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1>>C=CCOc1nc(-c2ccncc2)nc(NS(=O)(=O)Nc2ccc(C(C)C)cc2)c1Oc1ccccc1OC
ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC.C(C=C)O.C1CCOC1.[H-].[Na+]>>C(C=C)OC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC
[CH2:1]=[CH:2][CH2:3][OH:4].Cl[c:5]1[n:6][c:7](-[c:8]2[cH:9][cH:10][n:11][cH:12][cH:13]2)[n:14][c:15]([NH:16][S:17](=[O:18])(=[O:19])[NH:20][c:21]2[cH:22][cH:23][c:24]([CH:25]([CH3:26])[CH3:27])[cH:28][cH:29]2)[c:30]1[O:31][c:32]1[cH:33][cH:34][cH:35][cH:36][c:37]1[O:38][CH3:39]>>[CH2:1]=[CH:2][CH2:3][O:4][c:5]1[n:6][c...
C=CCO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1
C=CCOc1nc(-c2ccncc2)nc(NS(=O)(=O)Nc2ccc(C(C)C)cc2)c1Oc1ccccc1OC
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[#7:6]):[c:7]:1-[#8:8].[C;D1;H2:9]=[C:10]-[C:11]-[OH;D1;+0:12]>>[#7:6]-[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:12]-[C:11]-[C:10]=[C;D1;H2:9]):[c:7]:1-[#8:8]
null
[]
80
CELSIUS
null
null
To a mixture of allyl alcohol (1 ml) and THF (2 ml) was added sodium hydride (100 mg, 60% dispersion in mineral oil) followed by the addition of 4-i-propyl-phenyl sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (100 mg, Referential Example 1e)). DMF (0.5 ml) was added and the reaction m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1cncnc1.c1ccncc1.c1ccccc1.c1ccccc1
HCl
CN(C)C=O
80
null
C=CCO.COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1>CN(C)C=O>C=CCOc1nc(-c2ccncc2)nc(NS(=O)(=O)Nc2ccc(C(C)C)cc2)c1Oc1ccccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-dd381fa9f51b40b4a02d97a29218a03d
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1.OCCO>>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO
[H-].[Na+].C(CO)O.ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC>>OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:35]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][c:17]2[cH:18][cH:19][c:20]([CH:21]([CH3:22])[CH3:23])[cH:24][cH:25]2)[n:26][c:27](-[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[n:34]1.[OH:36][CH2:37][CH2:38][OH:39]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6]...
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1.OCCO
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO
null
null
C(OC)COC
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[#7:7]):[c:8]:1-[#8:9].[C:10]-[C:11]-[OH;D1;+0:12]>>[#7:7]-[c:6]1:[#7;a:5]:[c:3](-[c:4]):[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:12]-[C:11]-[C:10]):[c:8]:1-[#8:9]
null
[]
80
CELSIUS
30
MINUTE
Sodium hydride (17 mg, 60% dispersion in mineral oil) was added to ethylene glycol (1.2 ml) followed by addition of dimethoxyethane (0.5 ml). Stirring was continued for 30 min, then 4-i-propyl-phenyl sulfamic acid-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (45 mg, Referential Example 1e)) was ad...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1ccncc1
HCl
C(OC)COC
80
0.5
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1NS(=O)(=O)Nc1ccc(C(C)C)cc1.OCCO>C(OC)COC>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fd75d1250ff34f74a530d064642bf2d5
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncccn1>>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncccn1
CN(C)C=O.[H-].[Na+].OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC.ClC1=NC=CC=N1>>N1=C(N=CC=C1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][c:17]2[cH:18][cH:19][c:20]([CH:21]([CH3:22])[CH3:23])[cH:24][cH:25]2)[n:26][c:27](-[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[n:34][c:35]1[O:36][CH2:37][CH2:38][OH:39].Cl[c:40]1[n:41][cH:42][cH:43][cH:44][n:45]1>>...
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncccn1
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncccn1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)nc(OCCOc2ncccn2)c1Oc1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]
73
[{"value": 73.0, "product": "N1=C(N=CC=C1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
10
MINUTE
4-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (60 mg, Example 3) was dissolved in THF (8 ml) and sodium hydride (14 mg, 60% dispersion in mineral oil) was added and stirring continued for 10 min. 2-Chloro-pyrimidine (22 mg) was added and the mixture was h...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1ccncc1.c1cncnc1
HCl
C1CCOC1
60
0.166667
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncccn1>C1CCOC1>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a2a3024b09cf491db1828fcf80ec430e
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncc(Br)cn1>>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncc(Br)cn1
CN(C)C=O.OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC.[H-].[Na+].BrC=1C=NC(=NC1)Cl>>BrC=1C=NC(=NC1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][c:17]2[cH:18][cH:19][c:20]([CH:21]([CH3:22])[CH3:23])[cH:24][cH:25]2)[n:26][c:27](-[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[n:34][c:35]1[O:36][CH2:37][CH2:38][OH:39].Cl[c:40]1[n:41][cH:42][c:43]([Br:44])[cH:45][...
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncc(Br)cn1
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncc(Br)cn1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)nc(OCCOc2ncccn2)c1Oc1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]
71.9
[{"value": 71.9, "product": "BrC=1C=NC(=NC1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
10
MINUTE
4-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (60 mg, Example 3) was dissoved in THF (8 ml). Sodium hydride (14 mg, 60% dispersion in mineral oil) was added and stirring continued for 10 min. 5-Bromo-2-chloro-pyrimidine (37 mg) was added and the mixture w...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1ccncc1.c1cncnc1
HCl
C1CCOC1
60
0.166667
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.Clc1ncc(Br)cn1>C1CCOC1>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ncc(Br)cn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d0ced6154e874d9fa7cf2d92247c694c
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.FC(F)(F)c1ccc(Cl)nc1>>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ccc(C(F)(F)F)cn1
OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC.[H-].[Na+].FC(C=1C=CC(=NC1)Cl)(F)F>>FC(C=1C=CC(=NC1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC)(F)F
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][c:17]2[cH:18][cH:19][c:20]([CH:21]([CH3:22])[CH3:23])[cH:24][cH:25]2)[n:26][c:27](-[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[n:34][c:35]1[O:36][CH2:37][CH2:38][OH:39].Cl[c:40]1[cH:41][cH:42][c:43]([C:44]([F:45])(...
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.FC(F)(F)c1ccc(Cl)nc1
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ccc(C(F)(F)F)cn1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
ea617b323b892eda23f5ae30e789991ea9692064ef355a16e8ed81c16e743d2b
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1nc(-c2ccncc2)nc(OCCOc2ccccn2)c1Oc1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4]:[c:5]
64.9
[{"value": 64.9, "product": "FC(C=1C=CC(=NC1)OCCOC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NC1=CC=C(C=C1)C(C)C)(=O)=O)OC1=C(C=CC=C1)OC)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
10
MINUTE
4-i-Propyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidin-4-yl]-amide (50 mg, Example 3) was dissolved in THF (8 ml). Sodium hydride (12 mg, 60% dispersion in mineral oil) was added and stirring continued for 10 min. 5-Trifluoromethyl-2-chloro-pyridine (28 mg) was added and the ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccncc1
c1ccncc1
c1ccccc1.c1ccccc1.c1cncnc1.c1ccncc1.c1ccncc1
HCl
C1CCOC1
60
0.166667
COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCO.FC(F)(F)c1ccc(Cl)nc1>C1CCOC1>COc1ccccc1Oc1c(NS(=O)(=O)Nc2ccc(C(C)C)cc2)nc(-c2ccncc2)nc1OCCOc1ccc(C(F)(F)F)cn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-54c27a8b69d64090a7bc68f329ae5eb1
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.N>>COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl
ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1.N.N>>NC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1
Cl[c:11]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:22]([Cl:23])[n:21][c:14](-[c:15]2[cH:16][cH:17][n:18][cH:19][cH:20]2)[n:13]1.[NH3:12]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([NH2:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][cH:19][cH:20]2)[n:21][c:22]1[Cl:23]
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.N
COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl
null
null
O1CCOCC1
Heteroatom Alkylation and Arylation
OtherReaction
90f3138935f3ad06434c84a4ac47f6a17b2b61711b0b3fffea5d29513d5b1a76
c5668f64a1395fa45312378ed819baaeafc354cdb673b20226ea2853ed14db5d
c1ccc(Oc2cnc(-c3ccncc3)nc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9].[NH3;D0;+0:10]>>[#8:9]-[c:8]1:[c:6](-[Cl;D1;H0:7]):[#7;a:5]:[c:3](-[c:4]):[#7;a:2]:[c;H0;D3;+0:1]:1-[NH2;D1;+0:10]
null
[]
null
null
18
HOUR
4,6-Dichloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (2.9 g, Referential Example 1d)) was suspended in dioxane (30 ml) and ammonia (gaseous) was introduced until the solution was saturated. Stirring was continued for 7 days while the saturation of the reaction mixture with ammonia (gaseous) was repeated every 16 ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Primary amine
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccncc1
HCl
O1CCOCC1
null
18
COc1ccccc1Oc1c(Cl)nc(-c2ccncc2)nc1Cl.N>O1CCOCC1>COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-8747ffbddac545759a82510b3d14071c
CCNS(=O)(=O)Cl.COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl>>CCNS(=O)(=O)Nc1nc(-c2ccncc2)nc(Cl)c1Oc1ccccc1OC
NC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC=NC=C1.C1CCC2=NCCCN2CC1.C(C)NS(=O)(=O)Cl>>ClC1=C(C(=NC(=N1)C1=CC=NC=C1)NS(NCC)(=O)=O)OC1=C(C=CC=C1)OC
Cl[S:4]([NH:3][CH2:2][CH3:1])(=[O:5])=[O:6].[NH2:7][c:8]1[n:9][c:10](-[c:11]2[cH:12][cH:13][n:14][cH:15][cH:16]2)[n:17][c:18]([Cl:19])[c:20]1[O:21][c:22]1[cH:23][cH:24][cH:25][cH:26][c:27]1[O:28][CH3:29]>>[CH3:1][CH2:2][NH:3][S:4](=[O:5])(=[O:6])[NH:7][c:8]1[n:9][c:10](-[c:11]2[cH:12][cH:13][n:14][cH:15][cH:16]2)[n:17]...
CCNS(=O)(=O)Cl.COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl
CCNS(=O)(=O)Nc1nc(-c2ccncc2)nc(Cl)c1Oc1ccccc1OC
null
CN(C)C=1C=CN=CC1
C1CCOC1.C(Cl)Cl
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
79f8c5b4a38a78326b06fe818d16a864d10a3b32cd34e300057e08f5b58776e1
6630e3d6dc8a83d080e6361e8a6265158c2c9e15f17c9dff1184e40b54fc124d
c1ccc(Oc2cnc(-c3ccncc3)nc2)cc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[#7:4]-[C:5].[NH2;D1;+0:6]-[c:7]1:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1>>[C:5]-[#7:4]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[NH;D2;+0:6]-[c:7]1:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1
null
[]
null
null
12
HOUR
4-Amino-6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)-pyrimidine (100 mg) was dissolved in THF (5 ml) and DCM (5 ml). DBU (46 mg) and DMAP (37 mg) were added followed by the addition of ethyl-sulfamoylchloride (prepared from ethylamine hydrochloride and sulfuryl chloride). The mixture was stirred for 12 h at r.t. The sol...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Primary amine
Sulfonamide.Sulfonamide
null
null
c1cncnc1.c1ccncc1.c1ccccc1
HCl
CN(C)C=1C=CN=CC1.C1CCOC1.C(Cl)Cl
null
12
CCNS(=O)(=O)Cl.COc1ccccc1Oc1c(N)nc(-c2ccncc2)nc1Cl>CN(C)C=1C=CN=CC1.C1CCOC1.C(Cl)Cl>CCNS(=O)(=O)Nc1nc(-c2ccncc2)nc(Cl)c1Oc1ccccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-542f35727f4d4e29a5f0506e1410f87a
Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1.OCCO>>Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1
[Na].ClC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C.COCCOC.C(CO)O.[Na]>>OCCOC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C
Cl[c:15]1[n:14][cH:13][n:12][c:11]([NH:10][S:7]([NH:6][c:5]2[cH:4][cH:3][c:2]([CH3:1])[cH:29][cH:28]2)(=[O:8])=[O:9])[c:20]1-[c:21]1[cH:22][cH:23][c:24]([CH3:25])[cH:26][cH:27]1.[OH:16][CH2:17][CH2:18][OH:19]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][S:7](=[O:8])(=[O:9])[NH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][CH2:1...
Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1.OCCO
Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1ncncc1-c1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[#7:6]):[c:7]:1-[c:8].[C:9]-[C:10]-[OH;D1;+0:11]>>[#7:6]-[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:11]-[C:10]-[C:9]):[c:7]:1-[c:8]
null
[]
null
null
4
DAY
To a mixture of 1,2-dimethoxyethan (15 ml) and ethyleneglycol (40 ml) was added sodium (298 mg) in small portions. The mixture was stirred until the sodium was completely dissolved. Then DMF (15 ml), followed by 4-methyl-phenyl sulfamic acid-[6-chloro-5-(p-tolyl)-4-pyrimidinyl]-amide (1.0 g, Referential Example 14) was...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
CN(C)C=O
null
96
Cc1ccc(NS(=O)(=O)Nc2ncnc(Cl)c2-c2ccc(C)cc2)cc1.OCCO>CN(C)C=O>Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-10a552460a6a408ea1a49c7fdf62806f
Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1.Clc1ncc(Br)cn1>>Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCOc3ncc(Br)cn3)c2-c2ccc(C)cc2)cc1
C(CC(O)(C(=O)O)CC(=O)O)(=O)O.[H-].[Na+].OCCOC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C.BrC=1C=NC(=NC1)Cl>>BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][S:7](=[O:8])(=[O:9])[NH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][CH2:17][CH2:18][OH:19])[c:27]2-[c:28]2[cH:29][cH:30][c:31]([CH3:32])[cH:33][cH:34]2)[cH:35][cH:36]1.Cl[c:20]1[n:21][cH:22][c:23]([Br:24])[cH:25][n:26]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][S:7](=[O:8])(=[O:9])[NH:...
Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1.Clc1ncc(Br)cn1
Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCOc3ncc(Br)cn3)c2-c2ccc(C)cc2)cc1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(Nc1ccccc1)Nc1ncnc(OCCOc2ncccn2)c1-c1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]
52.5
[{"value": 52.5, "product": "BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NC1=CC=C(C=C1)C)(=O)=O)C1=CC=C(C=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To 4-methyl-phenyl sulfamic acid-[6-(2-hydroxy-ethoxy)-5-(p-tolyl)-4-pyrimidinyl]-amide (47 mg, Example 11) dissolved in THF (8 ml) was added sodium hydride (14.6 mg, 60% dispersion in mineral oil) and stirring was continued for 15 min followed by the addition of 5-bromo-2-chloro-pyrimidine (39 mg). Stirring was contin...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1cncnc1.c1ccccc1
HCl
C1CCOC1
null
0.25
Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCO)c2-c2ccc(C)cc2)cc1.Clc1ncc(Br)cn1>C1CCOC1>Cc1ccc(NS(=O)(=O)Nc2ncnc(OCCOc3ncc(Br)cn3)c2-c2ccc(C)cc2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-acd75006bb814bdab99020ebd9053b27
O=C(O)CC(O)(CC(=O)O)C(=O)O.O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1>>O=S(=O)(NCc1ccccc1)Nc1ncnc(OCCO)c1-c1ccc(Cl)cc1
CC(C)([O-])C.[K+].ClC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)C1=CC=C(C=C1)Cl.C(CC(O)(C(=O)O)CC(=O)O)(=O)O>>OCCOC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)C1=CC=C(C=C1)Cl
O=C(O)CC(C(=O)O)([OH:18])[CH2:19][C:20](=O)[OH:21].Cl[c:17]1[n:16][cH:15][n:14][c:13]([NH:12][S:2](=[O:1])(=[O:3])[NH:4][CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][cH:11]2)[c:22]1-[c:23]1[cH:24][cH:25][c:26]([Cl:27])[cH:28][cH:29]1>>[O:1]=[S:2](=[O:3])([NH:4][CH2:5][c:6]1[cH:7][cH:8][cH:9][cH:10][cH:11]1)[NH:12][c:13]1[n:14...
O=C(O)CC(O)(CC(=O)O)C(=O)O.O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1
O=S(=O)(NCc1ccccc1)Nc1ncnc(OCCO)c1-c1ccc(Cl)cc1
null
null
C(CO)O
Heteroatom Alkylation and Arylation
OtherReaction
b18ba87fb2ec0987a978e901bb5a53033e53fbf47b9296eda6a432ff7972ccf1
0d57d11c1ca6b9fbb36ccec54ea803b423eb00045b608c0a6b2fdbd90fbd86af
O=S(=O)(NCc1ccccc1)Nc1ncncc1-c1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[#7:6]):[c:7]:1-[c:8].O-C(=O)-C-C(-[OH;D1;+0:9])(-[CH2;D2;+0:10]-[C;H0;D3;+0:11](=O)-[O;D1;H1:12])-C(-O)=O>>[#7:6]-[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:9]-[CH2;D2;+0:10]-[CH2;D2;+0:11]-[O;D1;H1:12]):[c:7]:1-[c:8]
null
[]
102
CELSIUS
null
null
Potassium tert.-butoxide (3.5 g) was dissolved in ethyleneglycol (35 ml), benzyl sulfamic acid-[6-chloro-5-(4-chlorophenyl)-4-pyrimidinyl]-amide (1.8 g, Referential Example 15) was added and the mixture was heated to 102° C. for 11 h. The mixture was poured onto ice/water and acidified to pH=4 with solid citric acid. T...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carboxylic acid.Carboxylic acid.Carboxylic acid.Tertiary alcohol
Ether.Primary alcohol
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
C(CO)O
102
null
O=C(O)CC(O)(CC(=O)O)C(=O)O.O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1>C(CO)O>O=S(=O)(NCc1ccccc1)Nc1ncnc(OCCO)c1-c1ccc(Cl)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fbd7d5ace7f143329a76ff9d61c40004
COc1ccccc1Oc1c(Cl)nc(SC)nc1Cl.NS(=O)(=O)NCc1ccccc1>>COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1
ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)SC.[K].C(C1=CC=CC=C1)NS(N)(=O)=O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O>>ClC1=C(C(=NC(=N1)SC)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:18]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([Cl:12])[n:13][c:14]([S:15][CH3:16])[n:17]1.[NH2:19][S:20](=[O:21])(=[O:22])[NH:23][CH2:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([Cl:12])[n:13][c:14]([S:15][CH3:16])[n...
COc1ccccc1Oc1c(Cl)nc(SC)nc1Cl.NS(=O)(=O)NCc1ccccc1
COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(NCc1ccccc1)Nc1ncncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[#16:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9].[#7:10]-[#16:11](-[NH2;D1;+0:12])(=[O;D1;H0:13])=[O;D1;H0:14]>>[#16:4]-[c:3]1:[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8](-[#8:9]):[c;H0;D3;+0:1](-[NH;D2;+0:12]-[#16:11](-[#7:10])(=[O;D1;H0:13])=[O;D1;H0:14]):[#7;a:2]:1
79.2
[{"value": 79.2, "product": "ClC1=C(C(=NC(=N1)SC)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
18
HOUR
4,6-Dichloro-5-(2-methoxy-phenoxy)-2-methylsulfanyl-pyrimidine (1.5 g) was dissolved in DMSO (30 ml) and benzylsulfamic acid amide potassium salt (2.12 g, Referential Example 22) was added. Stirring was continued for 18 h. The reaction mixture was poured onto water, acidified by solid citric acid (1.9 g), cooled to 0° ...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
CS(=O)C
0
18
COc1ccccc1Oc1c(Cl)nc(SC)nc1Cl.NS(=O)(=O)NCc1ccccc1>CS(=O)C>COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-6ee78f80b18e4ed883b42873c9de4f88
COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1.O=C(O)CC(O)(CC(=O)O)C(=O)O>>COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(SC)nc1OCCO
ClC1=C(C(=NC(=N1)SC)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC.C(CC(O)(C(=O)O)CC(=O)O)(=O)O>>OCCOC1=C(C(=NC(=N1)SC)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:29]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][CH2:17][c:18]2[cH:19][cH:20][cH:21][cH:22][cH:23]2)[n:24][c:25]([S:26][CH3:27])[n:28]1.O=C(O)C(O)(C[C:31](=O)[OH:30])C[C:32](=O)[OH:33]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11...
COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1.O=C(O)CC(O)(CC(=O)O)C(=O)O
COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(SC)nc1OCCO
null
null
C(CO)O
Heteroatom Alkylation and Arylation
OtherReaction
b18ba87fb2ec0987a978e901bb5a53033e53fbf47b9296eda6a432ff7972ccf1
0d57d11c1ca6b9fbb36ccec54ea803b423eb00045b608c0a6b2fdbd90fbd86af
O=S(=O)(NCc1ccccc1)Nc1ncncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[#16:4]):[#7;a:5]:[c:6](-[#7:7]):[c:8]:1-[#8:9].O-C(=O)-C(-O)(-C-[C;H0;D3;+0:10](=O)-[OH;D1;+0:11])-C-[C;H0;D3;+0:12](=O)-[O;D1;H1:13]>>[#16:4]-[c:3]1:[#7;a:5]:[c:6](-[#7:7]):[c:8](-[#8:9]):[c;H0;D3;+0:1](-[O;H0;D2;+0:11]-[CH2;D2;+0:10]-[CH2;D2;+0:12]-[O;D1;H1:13]):[#7;a:2]:1
null
[]
100
CELSIUS
40
HOUR
Benzylsulfamic acid [6-chloro-5-(2-methoxy-phenoxy)-2-methylsulfanyl-pyrimidin-4-yl]-amide (1.75 g) was added to a solution of potassium tert.-butylate (1.87 g) in ethylene glycol (30 ml) and stirred at 100° C. for 40 h. The reaction mixture was poured onto water (120 ml), acidified with solid citric acid (1.9 g) and c...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carboxylic acid.Carboxylic acid.Carboxylic acid.Tertiary alcohol
Ether.Primary alcohol
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1
HCl
C(CO)O
100
40
COc1ccccc1Oc1c(Cl)nc(SC)nc1NS(=O)(=O)NCc1ccccc1.O=C(O)CC(O)(CC(=O)O)C(=O)O>C(CO)O>COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(SC)nc1OCCO
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c351c2e4f8214539a2c6c19c44d24359
C1COCCN1.COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(S(C)(=O)=O)nc1OCCO>>COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(N2CCOCC2)nc1OCCO
OCCOC1=C(C(=NC(=N1)S(=O)(=O)C)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC.N1CCOCC1.C(CC(O)(C(=O)O)CC(=O)O)(=O)O>>OCCOC1=C(C(=NC(=N1)N1CCOCC1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
[NH:26]1[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1.CS(=O)(=O)[c:25]1[n:24][c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][CH2:17][c:18]2[cH:19][cH:20][cH:21][cH:22][cH:23]2)[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:33]([O:34][CH2:35][CH2:36][OH:37])[n:32]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][...
C1COCCN1.COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(S(C)(=O)=O)nc1OCCO
COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(N2CCOCC2)nc1OCCO
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
a229bf13f557504c39a1f354abc763ba9cdeb25f6d32f8670bca8649cb0049f3
22da100633727aad1f507a5545a4789af97f1ba2143d8d6cef2b1c60e063c167
O=S(=O)(NCc1ccccc1)Nc1nc(N2CCOCC2)ncc1Oc1ccccc1
C-S(=O)(=O)-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1):[#7;a:4]:[c:5]
null
[]
45
CELSIUS
48
HOUR
Benzylsulfamic acid [6-(2-hydroxy-ethoxy)-2-methanesulfonyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amide (85 mg) were dissolved in THF (2 ml) and morpholine (2 ml) was added. The reaction mixture was stirred at 45° C. for 48 hours, poured onto water, acidified with solid citric acid and extracted with EtOAc (2×). The co...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfone
Tertiary amine
C1COCCN1.c1cncnc1
c1cncnc1.C1COCC[NH]1
c1ccccc1.c1ccccc1.c1cncnc1.C1COCC[NH]1
HO-
C1CCOC1
45
48
C1COCCN1.COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(S(C)(=O)=O)nc1OCCO>C1CCOC1>COc1ccccc1Oc1c(NS(=O)(=O)NCc2ccccc2)nc(N2CCOCC2)nc1OCCO
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-8294d5b564034b9ba886a31d576bed35
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1Cl.NS(=O)(=O)NCc1ccccc1>>COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1
C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(C)N(C(C)C)C(C)C.[K].C(C1=CC=CC=C1)NS(N)(=O)=O.ClC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)Cl)C1=CC(=NC=C1)C#N>>ClC1=C(C(=NC(=N1)C1=CC(=NC=C1)C#N)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
Cl[c:24]1[c:10]([O:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]2)[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][c:19]([C:20]#[N:21])[cH:22]2)[n:23]1.[NH2:25][S:26](=[O:27])(=[O:28])[NH:29][CH2:30][c:31]1[cH:32][cH:33][cH:34][cH:35][cH:36]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c...
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1Cl.NS(=O)(=O)NCc1ccccc1
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(NCc1ccccc1)Nc1nc(-c2ccncc2)ncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9].[#7:10]-[#16:11](-[NH2;D1;+0:12])(=[O;D1;H0:13])=[O;D1;H0:14]>>[#7:10]-[#16:11](=[O;D1;H0:13])(=[O;D1;H0:14])-[NH;D2;+0:12]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:1-[#8:9]
93
[{"value": 93.0, "product": "ClC1=C(C(=NC(=N1)C1=CC(=NC=C1)C#N)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
4-[4,6-Dichloro-5-(2-methoxy-phenoxy)-pyrimidin-2-yl]-pyridine-2-carbonitrile (3.2 g) was dissolved in DMSO (20 ml), N-ethyidiisopropylamine (1.7 ml) and benzylsulfamic acid amide potassium salt (3.52 g) was added. The mixture was stirred for 18 h at rt, poured onto ice/water, acidified with solid citric acid and the p...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccncc1.c1ccccc1
HCl
CS(=O)C
null
18
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1Cl.NS(=O)(=O)NCc1ccccc1>CS(=O)C>COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0b976c54799a443abc1b8ade62e50a2f
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1.[N-]=[N+]=[N-]>>COc1ccccc1Oc1c(Cl)nc(-c2ccnc(-c3nnn[nH]3)c2)nc1NS(=O)(=O)NCc1ccccc1
ClC1=C(C(=NC(=N1)C1=CC(=NC=C1)C#N)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC.[N-]=[N+]=[N-].[Na+].[Cl-].[NH4+]>>ClC1=C(C(=NC(=N1)C1=CC(=NC=C1)C1=NN=NN1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[O:9][c:10]1[c:11]([Cl:12])[n:13][c:14](-[c:15]2[cH:16][cH:17][n:18][c:19]([C:20]#[N:21])[cH:25]2)[n:26][c:27]1[NH:28][S:29](=[O:30])(=[O:31])[NH:32][CH2:33][c:34]1[cH:35][cH:36][cH:37][cH:38][cH:39]1.[N-:22]=[N+:23]=[N-:24]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8...
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1.[N-]=[N+]=[N-]
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(-c3nnn[nH]3)c2)nc1NS(=O)(=O)NCc1ccccc1
null
null
CN(C)C=O
Aromatic Heterocycle Formation
OtherReaction
237b84aaa459abf427f233dc6a07a1d9de824f980714e458423189bb68f60f12
d8c808528b7ee68720aaeebd35cb6a2a30e344748d0066102cdae99843b93cf0
O=S(=O)(NCc1ccccc1)Nc1nc(-c2ccnc(-c3nnn[nH]3)c2)ncc1Oc1ccccc1
[N-;H0;D1:1]=[N+;H0;D2:2]=[N-;H0;D1:3].[N;H0;D1;+0:4]#[C;H0;D2;+0:5]-[c;H0;D3;+0:6](:[#7;a:7]:[c:8]):[c:9]:[c:10]>>[c:10]:[c:9]:[c;H0;D3;+0:6](-[c;H0;D3;+0:5]1:[n;H0;D2;+0:4]:[n;H0;D2;+0:1]:[n;H0;D2;+0:2]:[nH;D2;+0:3]:1):[#7;a:7]:[c:8]
37
[{"value": 37.0, "product": "ClC1=C(C(=NC(=N1)C1=CC(=NC=C1)C1=NN=NN1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
20
HOUR
Benzylsulfamic acid [6-chloro-2-(2-cyano-pyridin-4-yl)-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amide (4.17 g) was dissolved in DMF (55 ml). Sodium azide (5.2 g) and ammonium chloride (4.28 g) were added and the mixture was stirred for 20 h at 80° C. Then the mixture was pored onto water and extracted with EtOAc. The laye...
10.6084/m9.figshare.5104873.v1
null
Nitrile
null
null
c1nnn[nH]1
c1ccccc1.c1cncnc1.c1ccncc1.c1nnn[nH]1.c1ccccc1
null
CN(C)C=O
80
20
COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)NCc1ccccc1.[N-]=[N+]=[N-]>CN(C)C=O>COc1ccccc1Oc1c(Cl)nc(-c2ccnc(-c3nnn[nH]3)c2)nc1NS(=O)(=O)NCc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-55d92de5fa0c4851ae06f9bff61c1f14
COc1ccc(Cl)c(OC(C(=O)O)C(=O)O)c1.N=CN>>COc1ccc(Cl)c(Oc2c(O)ncnc2O)c1
ClC1=C(OC(C(=O)O)C(=O)O)C=C(C=C1)OC.Cl.C(=N)N>>ClC1=C(OC=2C(=NC=NC2O)O)C=C(C=C1)OC
O=[C:11]([CH:10]([O:9][c:8]1[c:6]([Cl:7])[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:18]1)[C:16](=O)[OH:17])[OH:12].[NH:13]=[CH:14][NH2:15]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([O:9][c:10]2[c:11]([OH:12])[n:13][cH:14][n:15][c:16]2[OH:17])[cH:18]1
COc1ccc(Cl)c(OC(C(=O)O)C(=O)O)c1.N=CN
COc1ccc(Cl)c(Oc2c(O)ncnc2O)c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
b03631945f38bf302aeee4b9f74f85e65141b7a66cb69031caf004ec327f3dc0
31fac4e42cb8aa63b4d4c94f3c0d3cc94f37f20fca6f96719ed2a4be2a06cc7e
c1ccc(Oc2cncnc2)cc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[CH;D3;+0:3](-[#8:4]-[c:5])-[C;H0;D3;+0:6](=O)-[O;D1;H1:7].[NH2;D1;+0:8]-[CH;D2;+0:9]=[NH;D1;+0:10]>>[O;D1;H1:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:10]:[cH;D2;+0:9]:[n;H0;D2;+0:8]:[c;H0;D3;+0:6](-[O;D1;H1:7]):[c;H0;D3;+0:3]:1-[#8:4]-[c:5]
null
[]
null
null
null
null
5-(2-Chloro-5-methoxy-phenoxy)-pyrimidine-4,6-diol was prepared from 2-(2-chloro-5-methoxy-phenoxy)-malonic acid dimnethyl ster and formamidine hydrochloride according to the procedure described in Referential Example 1c. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Carboxylic acid.Ether.Primary amine
Ether.Aromatic alcohol.Aromatic alcohol
null
c1cncnc1
c1ccccc1.c1cncnc1
HO-
null
null
null
COc1ccc(Cl)c(OC(C(=O)O)C(=O)O)c1.N=CN>>COc1ccc(Cl)c(Oc2c(O)ncnc2O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-829e83a9265c4f86b928d2636b829e73
COc1ccc(Cl)c(Oc2c(Cl)ncnc2Cl)c1.NS(=O)(=O)NCc1ccccc1>>COc1ccc(Cl)c(Oc2c(Cl)ncnc2NS(=O)(=O)NCc2ccccc2)c1
ClC1=NC=NC(=C1OC1=C(C=CC(=C1)OC)Cl)Cl.[K].C(C1=CC=CC=C1)NS(N)(=O)=O>>ClC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl
Cl[c:16]1[c:10]([O:9][c:8]2[c:6]([Cl:7])[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:29]2)[c:11]([Cl:12])[n:13][cH:14][n:15]1.[NH2:17][S:18](=[O:19])(=[O:20])[NH:21][CH2:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([O:9][c:10]2[c:11]([Cl:12])[n:13][cH:14][n:15][c:16]2[NH:17][S:...
COc1ccc(Cl)c(Oc2c(Cl)ncnc2Cl)c1.NS(=O)(=O)NCc1ccccc1
COc1ccc(Cl)c(Oc2c(Cl)ncnc2NS(=O)(=O)NCc2ccccc2)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
345edf40ad678aea0250ec5b3d6cc512d8eac020b2f4324f423c18b59726753e
e7974806b40218fa965bb62bf9c430cac38870897b20726116f8b48ae128dc55
O=S(=O)(NCc1ccccc1)Nc1ncncc1Oc1ccccc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[#8:8].[#7:9]-[#16:10](-[NH2;D1;+0:11])(=[O;D1;H0:12])=[O;D1;H0:13]>>[#7:9]-[#16:10](=[O;D1;H0:12])(=[O;D1;H0:13])-[NH;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1-[#8:8]
47
[{"value": 47.0, "product": "ClC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Benzylsulfamic acid [6-chloro-5-(2-chloro-5-methoxy-phenoxy)-pyrimidin-4-yl]-amide (0.7 g) was prepared from 4,6-dichloro-5-(2-chloro-5-methoxy-phenoxy)-pyrimidine (1 g) and benzylsulfamic acid amide potassium salt (1.21 g) according to the procedure described in Referential Example 15. LC-MS: tR=5.13; [M+H]+=456.91. C...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Aromatic halide
Sulfonamide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1.c1ccccc1
HCl
null
null
null
COc1ccc(Cl)c(Oc2c(Cl)ncnc2Cl)c1.NS(=O)(=O)NCc1ccccc1>>COc1ccc(Cl)c(Oc2c(Cl)ncnc2NS(=O)(=O)NCc2ccccc2)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3bb0dfd1ce95456b8756fcc5434fcc41
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.Clc1ncc(Br)cn1>>COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(Br)cn2)c1
ClC1=C(OC=2C(=NC=NC2OCCO)NS(NCC2=CC=CC=C2)(=O)=O)C=C(C=C1)OC.BrC=1C=NC(=NC1)Cl>>BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([O:9][c:10]2[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][CH2:17][c:18]3[cH:19][cH:20][cH:21][cH:22][cH:23]3)[n:24][cH:25][n:26][c:27]2[O:28][CH2:29][CH2:30][OH:31])[cH:39]1.Cl[c:32]1[n:33][cH:34][c:35]([Br:36])[cH:37][n:38]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[...
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.Clc1ncc(Br)cn1
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(Br)cn2)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(NCc1ccccc1)Nc1ncnc(OCCOc2ncccn2)c1Oc1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]
48.4
[{"value": 48.4, "product": "BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-chloro-5-methoxy-phenoxy)-pyrimidin-4-yl]-amide (77 mg) (Example 212) was prepared from benzylsulfamic acid [5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-amide (120 mg) (Example 211) and 5-bromo-2-chloropyrimidine (100 mg) accordi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1cncnc1
HCl
null
null
null
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.Clc1ncc(Br)cn1>>COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(Br)cn2)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0557e87742a0462f9f27941c55dcda0f
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.CSc1cnc(Cl)nc1>>COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(SC)cn2)c1
ClC1=C(OC=2C(=NC=NC2OCCO)NS(NCC2=CC=CC=C2)(=O)=O)C=C(C=C1)OC.CSC=1C=NC(=NC1)Cl>>CSC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[c:8]([O:9][c:10]2[c:11]([NH:12][S:13](=[O:14])(=[O:15])[NH:16][CH2:17][c:18]3[cH:19][cH:20][cH:21][cH:22][cH:23]3)[n:24][cH:25][n:26][c:27]2[O:28][CH2:29][CH2:30][OH:31])[cH:40]1.Cl[c:32]1[n:33][cH:34][c:35]([S:36][CH3:37])[cH:38][n:39]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([...
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.CSc1cnc(Cl)nc1
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(SC)cn2)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=S(=O)(NCc1ccccc1)Nc1ncnc(OCCOc2ncccn2)c1Oc1ccccc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]
45.7
[{"value": 45.7, "product": "CSC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(NCC1=CC=CC=C1)(=O)=O)OC1=C(C=CC(=C1)OC)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Benzylsulfamic acid [6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-5-(2-chloro-5-methoxy-phenoxy)-pyrimidin-4-yl]-amide (138 mg) (Example 213) was prepared from benzylsulfamic acid [5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-amide (240 mg) (Example 211) and 5-methylsulfanyl-2-chloropyrimidi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1ccccc1.c1ccccc1.c1cncnc1.c1cncnc1
HCl
null
null
null
COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCO)c1.CSc1cnc(Cl)nc1>>COc1ccc(Cl)c(Oc2c(NS(=O)(=O)NCc3ccccc3)ncnc2OCCOc2ncc(SC)cn2)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e23d6a74247b400bb87430ce70adc43b
CCO.O=C(O)c1cc(F)c(F)c(F)c1F>>CCOC(=O)c1cc(F)c(F)c(F)c1F
C(=O)(O)[O-].[Na+].C(C)O.FC1=C(C(=O)O)C=C(C(=C1F)F)F.C(C(=O)Cl)(=O)Cl>>C(C)OC(C1=C(C(=C(C(=C1)F)F)F)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([F:13])[c:14]1[F:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([F:13])[c:14]1[F:15]
CCO.O=C(O)c1cc(F)c(F)c(F)c1F
CCOC(=O)c1cc(F)c(F)c(F)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
100.3
[{"value": 100.3, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
5
MINUTE
A solution of 2,3,4,5-tetrafluorobenzoic acid (4.68 g, 24.1 mmol) in dichloromethane (50 mL) at 0° C. is treated with oxalyl chloride (11.5 mL, 132 mmol) followed by N,N-dimethylformamide (4 drops). The mixture is stirred at 0° C. for 5 minutes and then at room temperature for 1.5 hours. The mixture is concentrated to ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
0
0.083333
CCO.O=C(O)c1cc(F)c(F)c(F)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(F)c(F)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-58a59fa4c9c44e9090ed4436fa020b49
CCO.O=C(O)c1c(F)cc(F)c(F)c1F>>CCOC(=O)c1c(F)cc(F)c(F)c1F
C(C)O.C(=O)(O)[O-].[Na+].C(C(=O)Cl)(=O)Cl.FC1=C(C(=O)O)C(=CC(=C1F)F)F>>C(C)OC(C1=C(C(=C(C=C1F)F)F)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[c:7]([F:8])[cH:9][c:10]([F:11])[c:12]([F:13])[c:14]1[F:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([F:8])[cH:9][c:10]([F:11])[c:12]([F:13])[c:14]1[F:15]
CCO.O=C(O)c1c(F)cc(F)c(F)c1F
CCOC(=O)c1c(F)cc(F)c(F)c1F
null
CN(C=O)C
ClCCl.C1=CC=CC=C1
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
60.1
[{"value": 60.1, "product": "C(C)OC(C1=C(C(=C(C=C1F)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
2,3,4,6-Tetrafluorobenzoic acid (4.8 g, 24.7 mmol) in dichloromethane (80 mL) is cooled to 0° C. under a nitrogen atmosphere and treated with oxalyl chloride (11.2 mL, 128 mmol) followed by anhydrous N,N-dimethylformamide (2 drops). The mixture is warmed to room temperature and stirred for 2 hours. The solution is co-e...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl.C1=CC=CC=C1
null
2
CCO.O=C(O)c1c(F)cc(F)c(F)c1F>CN(C=O)C.ClCCl.C1=CC=CC=C1>CCOC(=O)c1c(F)cc(F)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5a1e87024e2c4043be3cf1af09546602
CCO.O=C(O)c1cc(F)c(F)c(Cl)c1F>>CCOC(=O)c1cc(F)c(F)c(Cl)c1F
ClC=1C(=C(C(=O)O)C=C(C1F)F)F.C(C(=O)Cl)(=O)Cl.C(C)O>>C(C)OC(C1=C(C(=C(C(=C1)F)F)Cl)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([Cl:13])[c:14]1[F:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([Cl:13])[c:14]1[F:15]
CCO.O=C(O)c1cc(F)c(F)c(Cl)c1F
CCOC(=O)c1cc(F)c(F)c(Cl)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
100.6
[{"value": 100.6, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)F)Cl)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
To a solution of 3-chloro-2,4,5-trifluorobenzoic acid (Example 20, 4.90 g, 23.3 mmol) in dichloromethane (50 mL) is added oxalyl chloride (5.1 mL, 58.2 mmol) and N,N-dimethylformamide (1 drop). After 45 minutes, the reaction mixture is concentrated under vacuum. The resulting residue is dissolved in dichloromethane (50...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
null
0.75
CCO.O=C(O)c1cc(F)c(F)c(Cl)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(F)c(F)c(Cl)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0840a894e93d4828b9a71ddc2cef0484
O=C(O)c1c(F)c(F)c(F)c(F)c1F.OCc1ccccc1>>O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F
FC1=C(C(=O)O)C(=C(C(=C1F)F)F)F.C(C1=CC=CC=C1)O.Cl.CN(CCCN=C=NCC)C>>C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)F)F)F)=O
O[C:2](=[O:1])[c:11]1[c:12]([F:13])[c:14]([F:15])[c:16]([F:17])[c:18]([F:19])[c:20]1[F:21].[OH:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1>>[O:1]=[C:2]([O:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1)[c:11]1[c:12]([F:13])[c:14]([F:15])[c:16]([F:17])[c:18]([F:19])[c:20]1[F:21]
O=C(O)c1c(F)c(F)c(F)c(F)c1F.OCc1ccccc1
O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F
null
CN(C1=CC=NC=C1)C
ClCCl.[Cl-].[Na+].O
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
O=C(OCc1ccccc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[OH;D1;+0:6]-[C:7]-[c:8]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[O;H0;D2;+0:6]-[C:7]-[c:8])-[c:3](:[c:4]):[c:5]
77.3
[{"value": 77.3, "product": "C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
2
HOUR
A solution of 2,3,4,5,6-pentafluorobenzoic acid (15.25 g, 71.9 mmol), 4-dimethylaminopyridine (4.4 g, 36.0 mmol) and benzyl alcohol (7.4 mL, 71.5 mmol) in dichloromethane (150 mL) is cooled to 0° C. under an inert atmosphere. 1-[3-(Dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (16.7 g, 87.1 mmol) is added an...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.ClCCl.[Cl-].[Na+].O
0
2
O=C(O)c1c(F)c(F)c(F)c(F)c1F.OCc1ccccc1>CN(C1=CC=NC=C1)C.ClCCl.[Cl-].[Na+].O>O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3877a34e25a14eca872308956d9ca54b
CCO.O=C(O)c1cc(F)c(F)cc1F>>CCOC(=O)c1cc(F)c(F)cc1F
FC1=C(C(=O)O)C=C(C(=C1)F)F.C(C(=O)Cl)(=O)Cl.C(C)O>>C(C)OC(C1=C(C=C(C(=C1)F)F)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[cH:12][c:13]1[F:14]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[cH:12][c:13]1[F:14]
CCO.O=C(O)c1cc(F)c(F)cc1F
CCOC(=O)c1cc(F)c(F)cc1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
97.3
[{"value": 97.3, "product": "C(C)OC(C1=C(C=C(C(=C1)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
To a solution of 2,4,5-trifluorobenzoic acid (10.85 g, 61.6 mmol) in dichloromethane (100 mL) is added oxalyl chloride (13.5 mL, 154 mmol) and N,N-dimethylformamide (1 drop). After 45 minutes, the reaction mixture is concentrated under vacuum. The resulting residue is dissolved in dichloromethane (100 mL), and to this ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
null
0.75
CCO.O=C(O)c1cc(F)c(F)cc1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(F)c(F)cc1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-773f119220524fabb53ac3ee22baac20
CCO.COc1c(F)c(F)cc(C(=O)O)c1F>>CCOC(=O)c1cc(F)c(F)c(OC)c1F
C(=O)(O)[O-].[Na+].C(C)O.FC1=C(C(=O)O)C=C(C(=C1OC)F)F.C(C(=O)Cl)(=O)Cl>>C(C)OC(C1=C(C(=C(C(=C1)F)F)OC)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([O:13][CH3:14])[c:15]1[F:16]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([O:13][CH3:14])[c:15]1[F:16]
CCO.COc1c(F)c(F)cc(C(=O)O)c1F
CCOC(=O)c1cc(F)c(F)c(OC)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
98.8
[{"value": 98.8, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)F)OC)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
5
MINUTE
A solution of 2,4,5-trifluoro-3-methoxybenzoic acid (2.513 g, 12.19 mmol) in dichloromethane (50 mL) at 0° C. is treated with oxalyl chloride (5.4 mL, 61.9 mmol) followed by N,N-dimethylformamide (4 drops). The mixture is stirred at 0° C. for 5 minutes and then at room temperature for 2.5 hours. The mixture is concentr...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
0
0.083333
CCO.COc1c(F)c(F)cc(C(=O)O)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(F)c(F)c(OC)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1ce2e721306346368ed59e7d64aa7c46
CCO.O=C(O)c1ccc(F)c(F)c1F>>CCOC(=O)c1ccc(F)c(F)c1F
FC1=C(C(=O)O)C=CC(=C1F)F.C(C(=O)Cl)(=O)Cl.C(C)O>>C(C)OC(C1=C(C(=C(C=C1)F)F)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([F:10])[c:11]([F:12])[c:13]1[F:14]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([F:10])[c:11]([F:12])[c:13]1[F:14]
CCO.O=C(O)c1ccc(F)c(F)c1F
CCOC(=O)c1ccc(F)c(F)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
97.3
[{"value": 97.3, "product": "C(C)OC(C1=C(C(=C(C=C1)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
To a solution of 2,3,4-trifluorobenzoic acid (10.85 g, 61.6 mmol) in dichloromethane (100 mL) is added oxalyl chloride (13.5 mL, 154 mmol) and N,N-dimethylformamide (3 drops). After 45 minutes, the reaction mixture is concentrated under vacuum. The resulting residue is dissolved in dichloromethane (100 mL) and to this ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
null
0.75
CCO.O=C(O)c1ccc(F)c(F)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1ccc(F)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-49a5979b87634687b079fe6f0767adec
CCO.COc1cc(C(=O)O)c(F)c(F)c1F>>CCOC(=O)c1cc(OC)c(F)c(F)c1F
C(=O)(O)[O-].[Na+].C(C)O.FC1=C(C(=O)O)C=C(C(=C1F)F)OC.C(C(=O)Cl)(=O)Cl>>C(C)OC(C1=C(C(=C(C(=C1)OC)F)F)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([O:9][CH3:10])[c:11]([F:12])[c:13]([F:14])[c:15]1[F:16]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([O:9][CH3:10])[c:11]([F:12])[c:13]([F:14])[c:15]1[F:16]
CCO.COc1cc(C(=O)O)c(F)c(F)c1F
CCOC(=O)c1cc(OC)c(F)c(F)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
96.8
[{"value": 96.8, "product": "C(C)OC(C1=C(C(=C(C(=C1)OC)F)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3.5
HOUR
A solution of 2,3,4-trifluoro-5-methoxybenzoic acid (Hayashi et al., Bull. Chem. Soc. Jap., 1972; 45(9):2909–2914, 3.443 g, 16.7 mmol) in dichloromethane (100 mL) at 0° C. is treated with oxalyl chloride (7 mL, 80 mmol) followed by N,N-dimethylformamide (4 drops). The mixture is stirred at room temperature for 3.5 hour...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
null
3.5
CCO.COc1cc(C(=O)O)c(F)c(F)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(OC)c(F)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-94367b51827344b28aabf8e704d11349
CCO.Cc1c(F)c(F)cc(C(=O)O)c1F>>CCOC(=O)c1cc(F)c(F)c(C)c1F
C(=O)(O)[O-].[Na+].C(C)O.CC=1C(=C(C(=O)O)C=C(C1F)F)F.C(C(=O)Cl)(=O)Cl>>C(C)OC(C1=C(C(=C(C(=C1)F)F)C)F)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([CH3:13])[c:14]1[F:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([CH3:13])[c:14]1[F:15]
CCO.Cc1c(F)c(F)cc(C(=O)O)c1F
CCOC(=O)c1cc(F)c(F)c(C)c1F
null
CN(C=O)C
ClCCl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
77.1
[{"value": 77.1, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)F)C)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A solution of 3-methyl-2,4,5-trifluorobenzoic acid (Shimizu T., Asai T., Kumai S., Jpn. Kokai Tokkyo Koho (1997) Japanese Appl. JP 95-219069, 4.3 g, 22.6 mmol) in dichloromethane (100 mL) at 0° C. is treated with oxalyl chloride (4.2 g, 33 mmol) followed by N,N-dimethylformamide (2 drops). The mixture is stirred at roo...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
CN(C=O)C.ClCCl
null
3
CCO.Cc1c(F)c(F)cc(C(=O)O)c1F>CN(C=O)C.ClCCl>CCOC(=O)c1cc(F)c(F)c(C)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fe4ad7640e624dbfaf995746fd968f26
NOCc1ccccc1.O=Cc1c(F)c(F)cc(C(=O)O)c1F>>O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
Cl.FC1=C(C(=O)O)C=C(C(=C1C=O)F)F.C(C)N(CC)CC.Cl.C(C1=CC=CC=C1)ON>>C(C1=CC=CC=C1)ON=CC=1C(=C(C(=O)O)C=C(C1F)F)F
[NH2:12][O:13][CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.O=[CH:11][c:10]1[c:8]([F:9])[c:6]([F:7])[cH:5][c:4]([C:2](=[O:1])[OH:3])[c:21]1[F:22]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[c:10]([CH:11]=[N:12][O:13][CH2:14][c:15]2[cH:16][cH:17][cH:18][cH:19][cH:20]2)[c:21]1[F:22]
NOCc1ccccc1.O=Cc1c(F)c(F)cc(C(=O)O)c1F
O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
null
null
O1CCCC1.[Cl-].[Na+].O
Heteroatom Alkylation and Arylation
OtherReaction
54882f986dad145756472fc79464161665827db6af7b3780cb2b83c72b495424
3d6c7b6a0f29252ce5dcda36fa3ef05efc366c421f47850a88ae430c686fc79d
C(=NOCc1ccccc1)c1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[#8:6]-[NH2;D1;+0:7]>>[C:5]-[#8:6]-[N;H0;D2;+0:7]=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4]
100
[{"value": 100.0, "product": "C(C1=CC=CC=C1)ON=CC=1C(=C(C(=O)O)C=C(C1F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2,4,5-Trifluoro-3-formylbenzoic acid (Horiuchi N., Yonezawa T., Chiba K., Yoshida H., PCT Int. Appl. [1999] WO 97-JP2918), (5.70 g, 27.9 mmol), triethylamine (11 mL, 78.9 mmol), O-benzylhydroxylamine hydrochloride (4.47 g, 28.0 mmol) and anhydrous tetrahydrofuran (150 mL) are stirred at room temperature for 50 hours. T...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
null
null
null
c1ccccc1.c1ccccc1
HO-
O1CCCC1.[Cl-].[Na+].O
null
null
NOCc1ccccc1.O=Cc1c(F)c(F)cc(C(=O)O)c1F>O1CCCC1.[Cl-].[Na+].O>O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-86eb074600d544ca8411b5312724ec9d
CCO.O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F>>CCOC(=O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
C(C1=CC=CC=C1)ON=CC=1C(=C(C(=O)O)C=C(C1F)F)F.C(C)O.Cl.C(C)N=C=NCCCN(C)C>>C(C)OC(C1=C(C(=C(C(=C1)F)F)C=NOCC1=CC=CC=C1)F)=O
O[CH2:2][CH3:1].[OH:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([CH:13]=[N:14][O:15][CH2:16][c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2)[c:23]1[F:24]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]([CH:13]=[N:14][O:15][CH2:16][c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2)[c:2...
CCO.O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
CCOC(=O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
null
CN(C1=CC=NC=C1)C
ClCCl
Heteroatom Alkylation and Arylation
Esterification of Carboxylic Acids
3f9a9ace480b666da05fcfe5450d12b5c1ea5b0d435c195e1dd4bd20281604bb
dcbf04ec563ed0e9dfc79070490a028958024079a671c385858bb18cc8ec995a
C(=NOCc1ccccc1)c1ccccc1
O-[CH2;D2;+0:1]-[C;D1;H3:2].[O;D1;H0:3]=[C:4](-[OH;D1;+0:5])-[c:6]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[C:4](=[O;D1;H0:3])-[c:6]
53.3
[{"value": 53.3, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)F)C=NOCC1=CC=CC=C1)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
2
HOUR
3-(Benzyloxyiminomethyl)-2,4,5-trifluorobenzoic acid (0.117 g, 0.378 mmol), 4-dimethylaminopyridine (0.023 g, 0.189 mmol), anhydrous ethanol (0.030 mL, 0.517 mmol) are mixed in dichloromethane (6 mL), cooled to 0° C., and treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.082 g, 0.427 mmol). Af...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.ClCCl
0
2
CCO.O=C(O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F>CN(C1=CC=NC=C1)C.ClCCl>CCOC(=O)c1cc(F)c(F)c(C=NOCc2ccccc2)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5cc3631dde2a4f1db31e448dc5290720
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(F)c1F>>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
C(C)OC(C1=C(C(=C(C(=C1)F)F)F)F)=O.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O
[NH:11]1[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:26]([F:27])[c:24]1[F:25]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:...
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(F)c1F
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[C:10]-[C:11]-[NH;D2;+0:12]-1>>[F;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:12]1-[C:8]-[C:9]-[C:10]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
74.5
[{"value": 74.5, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2,3,4,5-tetrafluorobenzoic acid ethyl ester (Example 1a, 4.03 g, 18.1 mmol), (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.02 g, 21.6 mmol) (Sanchez J. P., Domagala J. M., Heifetz C. L., Priebe S. R., Sesnie J. A., Trehan A. K., J. Med. Chem., 1992; 35(10):1764–1773), and triethylamine (18.0 mL, 12...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(F)c1F>C(C)#N>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-acbacd71398448cdac9007290ea3a3a2
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1c(F)cc(F)c(F)c1F>>CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
C(C)OC(C1=C(C(=C(C=C1F)F)F)F)=O.C(C)N(CC)CC.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O>>C(C)OC(C1=C(C(=C(C=C1F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O
[NH:11]1[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[cH:9][c:7]([F:8])[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:26]([F:27])[c:24]1[F:25]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([F:8])[cH:9][c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:...
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1c(F)cc(F)c(F)c1F
CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6].[C:7]1-[C:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[F;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:7]-[C:8]-[C:9]-[C:10]-1):[c:2]:[c:3]
69.8
[{"value": 69.8, "product": "C(C)OC(C1=C(C(=C(C=C1F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2,3,4,6-tetrafluorobenzoic acid ethyl ester (Example 1b, 5.1 g, 22.9 mmol), triethylamine (22 mL, 157 mmol), and (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (5.2 g, 27.9 mmol) in acetonitrile (60 mL) is stirred at room temperature for 64 hours. The mixture is concentrated in vacuo and the residue di...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1c(F)cc(F)c(F)c1F>C(C)#N>CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2dd800356e8c4c8d8b56e82b571f1f7f
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F>>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F
C(C)OC(C1=C(C(=C(C(=C1)F)F)Cl)F)=O.C(C)N(CC)CC.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O>>C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)F)=O
[NH:11]1[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:26]([F:27])[c:24]1[Cl:25]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O...
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F
null
null
C(C)(=O)OCC.C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[Cl;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[C:10]-[C:11]-[NH;D2;+0:12]-1>>[Cl;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:12]1-[C:8]-[C:9]-[C:10]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
100.1
[{"value": 100.1, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
48
HOUR
To a solution of 3-chloro-2,4,5-trifluorobenzoic acid ethyl ester (Example 1c, 5.50 g, 23.05 mmol) in acetonitrile (25 mL) is added triethylamine (6.43 mL, 46.1 mmol) and (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.72 g, 25.4 mmol). After 48 hours, the mixture is diluted with ethyl acetate and washed with satu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)(=O)OCC.C(C)#N
null
48
CC(C)(C)OC(=O)N[C@H]1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F>C(C)(=O)OCC.C(C)#N>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0359e6b7f9d248c590d7dedd48f39951
CC(C)(C)OC(=O)N[C@H]1CCNC1.O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F>>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1
C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)F)F)F)=O.C(C)N(CC)CC.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O>>C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][NH:12][CH2:33]1.F[c:13]1[c:14]([F:15])[c:16]([F:17])[c:18]([C:19](=[O:20])[O:21][CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][cH:28]2)[c:29]([F:30])[c:31]1[F:32]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][N...
CC(C)(C)OC(=O)N[C@H]1CCNC1.O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=C(OCc1ccccc1)c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[F;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[C:12]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
63.6
[{"value": 63.6, "product": "C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2,3,4,5,6-pentafluorobenzoic acid benzyl ester (Example 1d, 8.05 g, 26.6 mmol), triethylamine (26 mL, 186 mmol), and (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (5.6 g, 30 mmol) in acetonitrile (150 mL) is stirred at room temperature for 24 hours. The solvent is removed under vacuum and the residue...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
C1CC[NH]C1.c1ccccc1
C1CC[NH]C1.c1ccccc1.c1ccccc1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.O=C(OCc1ccccc1)c1c(F)c(F)c(F)c(F)c1F>C(C)#N>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1240102ce85149d2a6f45262f5dded3b
C1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F>>CCOC(=O)c1cc(F)c(N2CCCC2)cc1F
C(C)OC(C1=C(C=C(C(=C1)F)F)F)=O.C(C)N(CC)CC.N1CCCC1>>C(C)OC(C1=C(C=C(C(=C1)F)N1CCCC1)F)=O
[NH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:17]([F:18])[cH:16]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH2:14][CH2:15]2)[cH:16][c:17]1[F:18]
C1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F
CCOC(=O)c1cc(F)c(N2CCCC2)cc1F
null
null
C(C)(=O)OCC.C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6].[C:7]1-[C:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[F;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:7]-[C:8]-[C:9]-[C:10]-1):[c:2]:[c:3]
97
[{"value": 97.0, "product": "C(C)OC(C1=C(C=C(C(=C1)F)N1CCCC1)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To a solution of 2,4,5-trifluorobenzoic acid ethyl ester (Example 1e, 4.32 g, 21.2 mmol) in acetonitrile (25 mL) is added triethylamine (5.9 mL, 42.3 mmol) and pyrrolidine (2.2 mL, 25.4 mmol). After 24 hours, the reaction mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The orga...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)(=O)OCC.C(C)#N
null
24
C1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F>C(C)(=O)OCC.C(C)#N>CCOC(=O)c1cc(F)c(N2CCCC2)cc1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f2ce1d24c4af410d90ca4f96147cdb48
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(OC)c1F>>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(OC)c1F
C(C)OC(C1=C(C(=C(C(=C1)F)F)OC)F)=O.C(C)(C)(C)OC(NC1CNCC1)=O.C(C)N(CC)CC>>C(C)OC(C1=C(C(=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)OC)F)=O
[NH:11]1[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:27]([F:28])[c:24]1[O:25][CH3:26]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:1...
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(OC)c1F
CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(OC)c1F
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[#8:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[C:10]-[C:11]-[NH;D2;+0:12]-1>>[#8:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:12]1-[C:8]-[C:9]-[C:10]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
77.6
[{"value": 77.6, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)OC)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2,4,5-trifluoro-3-methoxybenzoic acid ethyl ester (Example 1f, 2.821 g, 12.05 mmol), pyrrolidin-3-ylcarbamic acid tert-butyl ester (3.310 g, 17.77 mmol), and triethylamine (9.13 g, 12.6 mL, 90.23 mmol) in acetonitrile (50 mL) is heated at 40° C. under nitrogen for 2 days. The yellow solution is concentrat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(OC)c1F>C(C)#N>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(OC)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-61d96d89dc3346d09c856b21814d1a9f
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F>>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(Cl)c1F
C(C)OC(C1=C(C(=C(C(=C1)F)F)Cl)F)=O.C(C)N(CC)CC.C(C)(C)(C)OC(NC1CNCC1)=O>>C(C)OC(C1=C(C(=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)Cl)F)=O
[NH:11]1[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:26]([F:27])[c:24]1[Cl:25]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:1...
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F
CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(Cl)c1F
null
null
C(C)(=O)OCC.C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[Cl;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[C:10]-[C:11]-[NH;D2;+0:12]-1>>[Cl;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:12]1-[C:8]-[C:9]-[C:10]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
98.6
[{"value": 98.6, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)Cl)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
48
HOUR
To a solution of 3-chloro-2,4,5-tri-fluorobenzoic acid ethyl ester (Example 1c, 5.50 g, 23.05 mmol) in acetonitrile (25 mL) is added triethylamine (6.43 mL, 46.1 mmol) and pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.72 g, 25.4 mmol). After 48 hours, the mixture is diluted with ethyl acetate and washed with saturat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)(=O)OCC.C(C)#N
null
48
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)c(Cl)c1F>C(C)(=O)OCC.C(C)#N>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(Cl)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4cd038f4ec2c4063a2e06a388d2c39ee
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1ccc(F)c(F)c1F>>CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F
C(C)OC(C1=C(C(=C(C=C1)F)F)F)=O.C(C)(C)(C)OC(NC1CNCC1)=O.C(C)N(CC)CC>>C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)F)=O
[NH:10]1[CH2:11][CH2:12][CH:13]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])[CH2:22]1.F[c:9]1[cH:8][cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:25]([F:26])[c:23]1[F:24]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([N:10]2[CH2:11][CH2:12][CH:13]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:1...
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1ccc(F)c(F)c1F
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6].[C:7]1-[C:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[F;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:7]-[C:8]-[C:9]-[C:10]-1):[c:2]:[c:3]
70.1
[{"value": 70.1, "product": "C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2,3,4-trifluorobenzoic acid ethyl ester (Example 1g, 3.70 g, 18.1 mmol), pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.02 g, 21.6 mmol), and triethylamine (18.0 mL, 129 mmol) in acetonitrile (50 mL) is heated at 50° C. under nitrogen atmosphere for 4.5 hours. The solution is concentrated in vacuo and p...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1ccc(F)c(F)c1F>C(C)#N>CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0a282666be1a4e63bfa975c0f623bbd3
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F>>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F
C(C)OC(C1=C(C=C(C(=C1)F)F)F)=O.C(C)N(CC)CC.C(C)(C)(C)OC(NC1CNCC1)=O>>C(C)OC(C1=C(C=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)F)=O
[NH:11]1[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]1.F[c:10]1[c:8]([F:9])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:25]([F:26])[cH:24]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:1...
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F
CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F
null
null
C(C)(=O)OCC.C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6].[C:7]1-[C:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[F;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:7]-[C:8]-[C:9]-[C:10]-1):[c:2]:[c:3]
null
[]
null
null
45
HOUR
To a solution of 2,4,5-trifluorobenzoic acid ethyl ester (Example 1e, 14.8 g, 72.4 mmol) in acetonitrile (225 mL) is added triethylamine (65 mL, 466 mmol) and pyrrolidin-3-ylcarbamic acid tert-butyl ester (16.07 g, 86.2 mmol). After 45 hours, the reaction mixture is diluted with ethyl acetate and washed with saturated ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HF
C(C)(=O)OCC.C(C)#N
null
45
CC(C)(C)OC(=O)NC1CCNC1.CCOC(=O)c1cc(F)c(F)cc1F>C(C)(=O)OCC.C(C)#N>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0390ee46401f4971ae2800d3e2994491
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O.C1(CC1)N>>C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O
F[c:26]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[c:24]1[F:25].[NH2:27][CH:28]1[CH2:29][CH2:30]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]...
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(NC2CC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:2](-[F;D1;H0:3]):[c:4]
83
[{"value": 83.0, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,5-trifluorobenzoic acid ethyl ester (Example 2a, 1.95 g, 5.01 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in dimethyl sulfoxide (5 mL) is heated in a sealed glass tube for 44.5 hours at 100° C. Compressed air is blown into the black solution to re...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.C1CC1
HF
CS(=O)C
null
null
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>CS(=O)C>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-57255046f53942d386f59bb285a97248
CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>>CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
C(C)OC(C1=C(C(=C(C=C1F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O.C1(CC1)N>>C(C)OC(C1=C(C(=C(C=C1F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O
F[c:26]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:7]([F:8])[cH:9][c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[c:24]1[F:25].[NH2:27][CH:28]1[CH2:29][CH2:30]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([F:8])[cH:9][c:10]([N:11]2[CH2:12][CH2:13][C@H:14]...
CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1
CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(NC2CC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:2](-[F;D1;H0:3]):[c:4]
81.2
[{"value": 81.2, "product": "C(C)OC(C1=C(C(=C(C=C1F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester (Example 2b, 5.4 g, 13.9 mmol), cyclopropylamine (40 mL, 577 mmol), and dimethyl sulfoxide (28 mL) in a sealed glass tube is heated at 100° C. for 27 hours. The excess amine is removed by blowing in compressed air ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.C1CC1
HF
CS(=O)C
null
null
CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>CS(=O)C>CCOC(=O)c1c(F)cc(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-17cd02a021354dd183a83816d55b9074
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F.NC1CC1>>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1
C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)F)=O.C1(CC1)N.CS(=O)C>>C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)NC1CC1)=O
F[c:26]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[c:24]1[Cl:25].[NH2:27][CH:28]1[CH2:29][CH2:30]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14...
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F.NC1CC1
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1
null
null
C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(NC2CC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2](-[Cl;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:2](-[Cl;D1;H0:3]):[c:4]
43.2
[{"value": 43.2, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester (Example 2c, 9.34 g, 23.1 mmol), cyclopropylamine (16 mL, 228 mmol), and dimethyl sulfoxide (30 mL) is heated in a sealed tube at 110° C. for 3 days. After cooling to room temperature, the reaction mixture is...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.C1CC1
HF
C(C)(=O)OCC
null
null
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F.NC1CC1>C(C)(=O)OCC>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-bafe96c800354c5393ce9d00526fb0c7
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1.NC1CC1>>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(NC3CC3)c2F)C1
C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)F)=O.C1(CC1)N>>C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O
F[c:29]1[c:18]([C:19](=[O:20])[O:21][CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][cH:28]2)[c:16]([F:17])[c:14]([F:15])[c:13]([N:12]2[CH2:11][CH2:10][C@H:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:36]2)[c:34]1[F:35].[NH2:30][CH:31]1[CH2:32][CH2:33]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:...
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1.NC1CC1
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(NC3CC3)c2F)C1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=C(OCc1ccccc1)c1ccc(N2CCCC2)cc1NC1CC1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6]):[c:7]):[c:8](-[F;D1;H0:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[c:2](:[c:7]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:8](-[F;D1;H0:9]):[c:10]
86.2
[{"value": 86.2, "product": "C(C1=CC=CC=C1)OC(C1=C(C(=C(C(=C1F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,5,6-tetrafluorobenzoic acid benzyl ester (Example 2d, 2.5 g, 5.3 mmol), cyclopropylamine (40 mL, 577 mmol), and dimethyl sulfoxide (20 mL) in a sealed glass tube is heated at 80° C. for 24 hours. The excess amine is removed by blowing in compressed a...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
C1CC[NH]C1.c1ccccc1.c1ccccc1.C1CC1
HF
CS(=O)C
null
null
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(F)c2F)C1.NC1CC1>CS(=O)C>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c(C(=O)OCc3ccccc3)c(NC3CC3)c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f10a2f09cda54566ab1f1c06aa827088
CC(C)N.CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F>>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1NC(C)C
C(C)OC(C1=C(C=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)F)=O.C(C)(C)N>>C(C)OC(C1=C(C=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)NC(C)C)=O
[NH2:26][CH:27]([CH3:28])[CH3:29].F[c:25]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[cH:24]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15...
CC(C)N.CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F
CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1NC(C)C
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8]):[c:9].[C;D1;H3:10]-[C:11](-[C;D1;H3:12])-[NH2;D1;+0:13]>>[C:8]-[#8:7]-[C:5](=[O;D1;H0:6])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:13]-[C:11](-[C;D1;H3:10])-[C;D1;H3:12]):[c:2]:[c:3]
28.1
[{"value": 28.1, "product": "C(C)OC(C1=C(C=C(C(=C1)F)N1CC(CC1)NC(=O)OC(C)(C)C)NC(C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-[3-(tert-Butoxycarbonylamino)-pyrrolidin-1-yl]-2,5-difluorobenzoic acid ethyl ester (Example 2j, 5.4 g, 13.9 mmol), isopropylamine (40 mL, 469 mmol), and dimethyl sulfoxide (25 mL) are heated at 100° C. for 4 days in a sealed glass tube. The excess amine is removed by blowing in compressed air. The residue is filtere...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1
HF
CS(=O)C
null
null
CC(C)N.CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1F>CS(=O)C>CCOC(=O)c1cc(F)c(N2CCC(NC(=O)OC(C)(C)C)C2)cc1NC(C)C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c9ad7ba81a844b13b2fa7d7f9fd4ed34
CCC(C)N.CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F>>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC(C)CC
C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)F)=O.C(C)(CC)N>>C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)NC(C)CC)=O
[NH2:27][CH:28]([CH3:29])[CH2:30][CH3:31].F[c:26]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13][C@H:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[c:24]1[Cl:25]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([N:11]2[CH2:12][CH2:13...
CCC(C)N.CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC(C)CC
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(N2CCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[Cl;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[C:11]-[C:12](-[C;D1;H3:13])-[NH2;D1;+0:14]>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:14]-[C:12](-[C:11])-[C;D1;H3:13]):[c:2](-[Cl;D1;H0:3]):[c:4]
167.5
[{"value": 167.5, "product": "C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)NC(C)CC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester (Example 2c, 1.95 g, 4.81 mmol), sec-butylamine (30 mL, 296 mmol), and dimethyl sulfoxide (20 mL) are heated in a sealed glass tube at 110° C. for 24 hours. The reaction mixture is evaporated, and purification by column ch...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1
HF
CS(=O)C
null
null
CCC(C)N.CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1F>CS(=O)C>CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC(C)CC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c69cc9c8887b40f49bc3a26eadc7f8aa
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>>CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)F)=O.C1(CC1)N>>C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O
F[c:25]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][cH:8][c:9]([N:10]2[CH2:11][CH2:12][CH:13]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])[CH2:22]2)[c:23]1[F:24].[NH2:26][CH:27]1[CH2:28][CH2:29]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([N:10]2[CH2:11][CH2:12][CH:13]([NH:14][C:15](=...
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
null
null
CN(C(C)=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(NC2CC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:2](-[F;D1;H0:3]):[c:4]
76.9
[{"value": 76.9, "product": "C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3-difluorobenzoic acid ethyl ester (Example 2h, 1.85 g, 5.01 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in N,N-dimethylacetamide (5 mL) is heated in a sealed glass tube for 48 hours at 100° C. The solution is then concentrated under high vacuum and pur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.C1CC1
HF
CN(C(C)=O)C
null
null
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>CN(C(C)=O)C>CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-04ac14ea81ab4703950b7e11ba716028
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>>CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
C(C)OC(C1=C(C(=C(C(=C1)Cl)N1CC(CC1)NC(=O)OC(C)(C)C)F)F)=O.C1(CC1)N>>C(C)OC(C1=C(C(=C(C(=C1)Cl)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O
F[c:26]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([Cl:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:23]2)[c:24]1[F:25].[NH2:27][CH:28]1[CH2:29][CH2:30]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([Cl:9])[c:10]([N:11]2[CH2:12][CH2:13][CH:14]...
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
null
null
CN(C(C)=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(NC2CC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9]):[c:10].[NH2;D1;+0:11]-[C:12]1-[C:13]-[C:14]-1>>[C:9]-[#8:8]-[C:6](=[O;D1;H0:7])-[c:5](:[c:10]):[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:2](-[F;D1;H0:3]):[c:4]
48.7
[{"value": 48.7, "product": "C(C)OC(C1=C(C(=C(C(=C1)Cl)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2,3-difluorobenzoic acid ethyl ester (Example 21, 3.75 g, 9.3 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in N,N-dimethylacetamide (5 mL) is heated in a sealed glass tube for 48 hours at 100° C. The solution is then concentrated under high vacuum...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.C1CC1
HF
CN(C(C)=O)C
null
null
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1F.NC1CC1>CN(C(C)=O)C>CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ad384940417e4d18b0bae0170e802d31
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1>>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)cc(C(=O)O)c(NC3CC3)c2Cl)C1
C(C)OC(C1=C(C(=C(C(=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)Cl)NC1CC1)=O.[OH-].[Na+]>>C(C)(C)(C)OC(=O)N[C@@H]1CN(CC1)C1=C(C(=C(C(=O)O)C=C1F)NC1CC1)Cl
CC[O:20][C:18]([c:17]1[cH:16][c:14]([F:15])[c:13]([N:12]2[CH2:11][CH2:10][C@H:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:28]2)[c:26]([Cl:27])[c:21]1[NH:22][CH:23]1[CH2:24][CH2:25]1)=[O:19]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][N:12]([c:13]2[c:14]([F:15])[cH:...
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)cc(C(=O)O)c(NC3CC3)c2Cl)C1
null
null
CO.C(C)(=O)OCC.O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1cc(NC2CC2)cc(N2CCCC2)c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
null
[]
80
CELSIUS
20
HOUR
To a solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2-cyclopropylamino-5-fluorobenzoic acid ethyl ester (Example 3c, 2.90 g, 6.56 mmol) in methanol (30 mL) and tetrahydrofuran (30 mL) is added a 1N solution of sodium hydroxide (50 mL). The reaction mixture is stirred at 80° C. for 20 hours, co...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]C1.c1ccccc1.C1CC1
Other
CO.C(C)(=O)OCC.O1CCCC1
80
20
CCOC(=O)c1cc(F)c(N2CC[C@H](NC(=O)OC(C)(C)C)C2)c(Cl)c1NC1CC1>CO.C(C)(=O)OCC.O1CCCC1>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)cc(C(=O)O)c(NC3CC3)c2Cl)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ce8ce431edd04053a879283a27982b23
CCOC(=O)c1cc(F)c(N2CCCC2)cc1NC1CC1>>O=C(O)c1cc(F)c(N2CCCC2)cc1NC1CC1
C(C)OC(C1=C(C=C(C(=C1)F)N1CCCC1)NC1CC1)=O.[OH-].[Na+]>>C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)N1CCCC1)F
CC[O:3][C:2](=[O:1])[c:4]1[cH:5][c:6]([F:7])[c:8]([N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][c:15]1[NH:16][CH:17]1[CH2:18][CH2:19]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][c:15]1[NH:16][CH:17]1[CH2:18][CH2:19]1
CCOC(=O)c1cc(F)c(N2CCCC2)cc1NC1CC1
O=C(O)c1cc(F)c(N2CCCC2)cc1NC1CC1
null
null
CO.C(C)(=O)OCC.O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1cc(NC2CC2)cc(N2CCCC2)c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
89.9
[{"value": 89.9, "product": "C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)N1CCCC1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
20
HOUR
To a solution of 4-(pyrrolidin-1-yl)-2-cyclopropylamino-5-fluorobenzoic acid ethyl ester (Example 3e, 3.10 g, 10.4 mmol) in methanol (50 mL) and tetrahydrofuran (20 mL) is added 1N solution of sodium hydroxide (35 mL). The reaction mixture is stirred at 80° C. for 20 hours, cooled to room temperature, and diluted with ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.C1CC[NH]C1.C1CC1
Other
CO.C(C)(=O)OCC.O1CCCC1
80
20
CCOC(=O)c1cc(F)c(N2CCCC2)cc1NC1CC1>CO.C(C)(=O)OCC.O1CCCC1>O=C(O)c1cc(F)c(N2CCCC2)cc1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-389f49bf74d24494a85a7b0e9addedb2
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1>>CC(C)(C)OC(=O)NC1CCN(c2ccc(C(=O)O)c(NC3CC3)c2F)C1
C(C)OC(C1=C(C(=C(C=C1)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O.[OH-].[Na+]>>C(C)(C)(C)OC(=O)NC1CN(CC1)C1=C(C(=C(C(=O)O)C=C1)NC1CC1)F
CC[O:19][C:17]([c:16]1[cH:15][cH:14][c:13]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:27]2)[c:25]([F:26])[c:20]1[NH:21][CH:22]1[CH2:23][CH2:24]1)=[O:18]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH:15][c:16]([C:17](...
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
CC(C)(C)OC(=O)NC1CCN(c2ccc(C(=O)O)c(NC3CC3)c2F)C1
null
null
CO.O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1cc(NC2CC2)cc(N2CCCC2)c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
112.2
[{"value": 112.2, "product": "C(C)(C)(C)OC(=O)NC1CN(CC1)C1=C(C(=C(C(=O)O)C=C1)NC1CC1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2-cyclopropylamino-3-fluorobenzoic acid ethyl ester (Example 3j, 1.34 g, 3.29 mmol) and aqueous sodium hydroxide (2N, 20 mL) in tetrahydrofuran (20 mL) and methanol (20 mL) is refluxed for 1 hour. The solution is partially concentrated in vacuo, then acidifi...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]C1.c1ccccc1.C1CC1
Other
CO.O1CCCC1
null
null
CCOC(=O)c1ccc(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1>CO.O1CCCC1>CC(C)(C)OC(=O)NC1CCN(c2ccc(C(=O)O)c(NC3CC3)c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a7f356a059ad4e31955c0bb42ee06496
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1>>CC(C)(C)OC(=O)NC1CCN(c2c(Cl)cc(C(=O)O)c(NC3CC3)c2F)C1
C(C)OC(C1=C(C(=C(C(=C1)Cl)N1CC(CC1)NC(=O)OC(C)(C)C)F)NC1CC1)=O.[OH-].[Na+].CO>>C(C)(C)(C)OC(=O)NC1CN(CC1)C1=C(C(=C(C(=O)O)C=C1Cl)NC1CC1)F
CC[O:20][C:18]([c:17]1[cH:16][c:14]([Cl:15])[c:13]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:28]2)[c:26]([F:27])[c:21]1[NH:22][CH:23]1[CH2:24][CH2:25]1)=[O:19]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][N:12]([c:13]2[c:14]([Cl:15])[cH:1...
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1
CC(C)(C)OC(=O)NC1CCN(c2c(Cl)cc(C(=O)O)c(NC3CC3)c2F)C1
null
null
O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1cc(NC2CC2)cc(N2CCCC2)c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
91.3
[{"value": 91.3, "product": "C(C)(C)(C)OC(=O)NC1CN(CC1)C1=C(C(=C(C(=O)O)C=C1Cl)NC1CC1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2-cyclopropylamino-3-fluorobenzoic acid ethyl ester (Example 3k, 2.00 g, 4.50 mmol) and aqueous sodium hydroxide (2.0N, 20 mL) in tetrahydrofuran (20 mL), and methanol (20 mL) is refluxed for 1 hour. The solution is partially concentrated in vacuo, ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]C1.c1ccccc1.C1CC1
Other
O1CCCC1
null
null
CCOC(=O)c1cc(Cl)c(N2CCC(NC(=O)OC(C)(C)C)C2)c(F)c1NC1CC1>O1CCCC1>CC(C)(C)OC(=O)NC1CCN(c2c(Cl)cc(C(=O)O)c(NC3CC3)c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c17e0a2a9f6b4b76a94d85708a9a1372
CCOC1(O[Si](C)(C)C)CC1.Nc1cc(F)c(F)cc1C(=O)O>>O=C(O)c1cc(F)c(F)cc1NC1CC1
C(#N)[BH3-].[Na+].FC=1C=C(C(C(=O)O)=CC1F)N.C(C)(=O)O.C(C)OC1(CC1)O[Si](C)(C)C>>C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)F)F
CCO[C:13]1(O[Si](C)(C)C)[CH2:14][CH2:15]1.[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10][c:11]1[NH2:12]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10][c:11]1[NH:12][CH:13]1[CH2:14][CH2:15]1
CCOC1(O[Si](C)(C)C)CC1.Nc1cc(F)c(F)cc1C(=O)O
O=C(O)c1cc(F)c(F)cc1NC1CC1
null
null
CO.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
OtherReaction
98d8dfe2826a8c6338bf96b49d186b191d9599236f93ee5c29e87c823fb798b6
ee949e00a6e6830a378056a2b6ec30dca5828fadb846505c80425caa906dfa25
c1ccc(NC2CC2)cc1
C-C-O-[C;H0;D4;+0:1]1(-O-[Si](-C)(-C)-C)-[C:2]-[C:3]-1.[NH2;D1;+0:4]-[c:5](:[c:6]):[c:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]>>[O;D1;H0:9]=[C:8](-[O;D1;H1:10])-[c:7]:[c:5](-[NH;D2;+0:4]-[CH;D3;+0:1]1-[C:2]-[C:3]-1):[c:6]
94.8
[{"value": 94.8, "product": "C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of 4,5-difluoroanthranilic acid (1.13 g, 6.53 mmol) in anhydrous methanol (40 mL) is added molecular sieves (3 Å), acetic acid (3.70 mL, 65.3 mmol) and [(1-ethoxycyclopropyl)oxy]trimethylsilane (5.25 mL, 26.11 mmol). After 30 minutes, sodium cyanoborohydride (2.08 g, 32.64 mmol) is added, and the reaction...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine.Silyl protective group
Secondary amine
C1CC1
C1CC1
c1ccccc1.C1CC1
HO-
CO.C(C)(=O)OCC
null
0.5
CCOC1(O[Si](C)(C)C)CC1.Nc1cc(F)c(F)cc1C(=O)O>CO.C(C)(=O)OCC>O=C(O)c1cc(F)c(F)cc1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0123970af20b4d508cbf2eed15a3b1af
Nc1ccc(F)cc1F.O=C(O)c1cc(F)c(F)cc1F>>O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
C(C)(C)[N-]C(C)C.[Li+].FC1=C(C(=O)O)C=C(C(=C1)F)F.C(CCC)[Li].FC1=C(N)C=CC(=C1)F.Cl.O1CCOCC1.C(C)(C)NC(C)C>>FC1=C(NC2=C(C(=O)O)C=C(C(=C2)F)F)C=CC(=C1)F
[NH2:12][c:13]1[cH:14][cH:15][c:16]([F:17])[cH:18][c:19]1[F:20].F[c:11]1[c:4]([C:2](=[O:1])[OH:3])[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10][c:11]1[NH:12][c:13]1[cH:14][cH:15][c:16]([F:17])[cH:18][c:19]1[F:20]
Nc1ccc(F)cc1F.O=C(O)c1cc(F)c(F)cc1F
O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[O;D1;H1:7]):[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[O;D1;H0:6]=[C:5](-[O;D1;H1:7])-[c:4](:[c:8]):[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:2]:[c:3]
45
[{"value": 45.0, "product": "FC1=C(NC2=C(C(=O)O)C=C(C(=C2)F)F)C=CC(=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-78
CELSIUS
0.5
HOUR
Lithium diisopropylamide is generated at −5° C. by combining diisopropylamine (7.2 mL, 51 mmol) and n-butyllithium (33 mL, 53 mmol) in anhydrous tetrahydrofuran (150 mL) under an inert atmosphere. After 0.5 hour, the solution is cooled to −78° C. and 2,4-difluoroaniline (3.46 mL, 34 mmol) is added and stirred for 2 hou...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
O1CCCC1
-78
0.5
Nc1ccc(F)cc1F.O=C(O)c1cc(F)c(F)cc1F>O1CCCC1>O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ab04c13734c14f0eb76b4fd42879a70a
NC1CC1.O=C(O)c1cc(F)c(F)c(Cl)c1Br>>O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1
BrC1=C(C(=O)O)C=C(C(=C1Cl)F)F.C1(CC1)N.C(C)(=O)[O-].[K+].C(C)N(CC)CC>>ClC=1C(=C(C(=O)O)C=C(C1F)F)NC1CC1
[NH2:13][CH:14]1[CH2:15][CH2:16]1.Br[c:12]1[c:4]([C:2](=[O:1])[OH:3])[cH:5][c:6]([F:7])[c:8]([F:9])[c:10]1[Cl:11]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[c:10]([Cl:11])[c:12]1[NH:13][CH:14]1[CH2:15][CH2:16]1
NC1CC1.O=C(O)c1cc(F)c(F)c(Cl)c1Br
O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NC2CC2)cc1
Br-[c;H0;D3;+0:1](:[c:2](-[Cl;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9].[NH2;D1;+0:10]-[C:11]1-[C:12]-[C:13]-1>>[Cl;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C:11]1-[C:12]-[C:13]-1):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9]
63.7
[{"value": 63.7, "product": "ClC=1C(=C(C(=O)O)C=C(C1F)F)NC1CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
16
HOUR
In a sealed tube a mixture of 2-bromo-3-chloro-4,5-difluorobenzoic acid (Example 20, 7.96 g, 29.3 mmol), cyclopropyl amine (4.20 mL, 58.7 mmol), potassium acetate (5.77 g, 58.6 mmol), cupric acetate monohydrate (0.50 g, 2.5 mmol), and triethylamine (4.9 mL, 35.19 mmol) in isopropyl alcohol is stirred at 80° C. After 16...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC1
HBr
C(C)(C)O
80
16
NC1CC1.O=C(O)c1cc(F)c(F)c(Cl)c1Br>C(C)(C)O>O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d6dea635e510434eb027e992714d250b
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1NC1CC1>>CC(C)(C)OC(=O)NNC(=O)c1cc(F)c(F)cc1NC1CC1
C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)F)F.C(NN)(=O)OC(C)(C)C.C(C)N=C=NCCCN(C)C>>C(C)(C)(C)OC(=O)NNC(C1=C(C=C(C(=C1)F)F)NC1CC1)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][NH2:9].O[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[cH:18][c:19]1[NH:20][CH:21]1[CH2:22][CH2:23]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][NH:9][C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[cH:18][c:19]1[NH:20][CH:21]1[CH2:2...
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1NC1CC1
CC(C)(C)OC(=O)NNC(=O)c1cc(F)c(F)cc1NC1CC1
null
null
ClCCl
Acylation
Carboxylic acid with primary amine to amide
1bfc5046b360bb38c235d234cdd252f03d34a0792ef57a2cdb032482310d9689
1f93e2b4a6ed796a4645f0486672499ca332a9bc5c180e504c9a46d8eb8d844d
c1ccc(NC2CC2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[#7:13]-[NH2;D1;+0:14]>>[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[#7:13]-[NH;D2;+0:14]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
81.4
[{"value": 81.4, "product": "C(C)(C)(C)OC(=O)NNC(C1=C(C=C(C(=C1)F)F)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of 2-cyclopropylamino-4,5-difluorobenzoic acid (Example 5) (1.32 g, 6.19 mmol) and tert-butyl carbazate (1.30 g, 9.75 mmol) in dichloromethane (30 mL) is added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (1.87 g, 9.75 mmol). After 16 hours, the reaction mixture is diluted with dichloromethane and washe...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Carboxylic acid
Acylhydrazine.Acylhydrazine
null
null
c1ccccc1.C1CC1
HO-
ClCCl
null
16
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1NC1CC1>ClCCl>CC(C)(C)OC(=O)NNC(=O)c1cc(F)c(F)cc1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-eeeb0d9ca8654a97b94c5952a45d29e4
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F>>CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
FC1=C(NC2=C(C(=O)O)C=C(C(=C2)F)F)C=CC(=C1)F.C(NN)(=O)OC(C)(C)C.C(C)N=C=NCCCN(C)C>>C(C)(C)(C)OC(=O)N(N)C(C1=C(C=C(C(=C1)F)F)NC1=C(C=C(C=C1)F)F)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][NH2:9].O[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[cH:18][c:19]1[NH:20][c:21]1[cH:22][cH:23][c:24]([F:25])[cH:26][c:27]1[F:28]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([NH2:9])[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[cH...
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
null
null
ClCCl
Protection
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
c98ee5b7ab674ace8788dc72836dff1f14049f74d05f98c07e40c7e2dbb84b79
ad033db82ebb2e7a535de94b1f0f3d4f69c3d8512618c4288ab7622a9f6af1cc
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[NH;D2;+0:13]-[N;D1;H2:14]>>[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[N;H0;D3;+0:13](-[N;D1;H2:14])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
72.5
[{"value": 72.5, "product": "C(C)(C)(C)OC(=O)N(N)C(C1=C(C=C(C(=C1)F)F)NC1=C(C=C(C=C1)F)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of 2-(2,4-difluoroanilino)-4,5-difluorobenzoic acid (Example 5, 2.18 g, 7.6 mmol) and tert-butyl carbazate (1.57 g, 11.8 mmol) in dichloromethane (30 mL) is added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (2.25 g, 11.77 mmol). After stirring for 16 hours at room temperature, the reaction mixture is d...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Carbamic ester.Carboxylic acid
Acylhydrazine.Acylhydrazine
null
null
c1ccccc1.c1ccccc1
HO-
ClCCl
null
16
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F>ClCCl>CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)cc1Nc1ccc(F)cc1F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2215a032e5f9454f83cc5b8245d8b56f
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1>>CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1
ClC=1C(=C(C(=O)O)C=C(C1F)F)NC1CC1.C(NN)(=O)OC(C)(C)C.C(C)N=C=NCCCN(C)C>>C(C)(C)(C)OC(=O)N(N)C(C1=C(C(=C(C(=C1)F)F)Cl)NC1CC1)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][NH2:9].O[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[c:18]([Cl:19])[c:20]1[NH:21][CH:22]1[CH2:23][CH2:24]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([NH2:9])[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[c:18]([Cl:19])[c:20]1[NH...
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1
CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1
null
null
ClCCl
Protection
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
c98ee5b7ab674ace8788dc72836dff1f14049f74d05f98c07e40c7e2dbb84b79
ad033db82ebb2e7a535de94b1f0f3d4f69c3d8512618c4288ab7622a9f6af1cc
c1ccc(NC2CC2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[NH;D2;+0:13]-[N;D1;H2:14]>>[C;D1;H3:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[#8:10]-[C:11](=[O;D1;H0:12])-[N;H0;D3;+0:13](-[N;D1;H2:14])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
63.1
[{"value": 63.1, "product": "C(C)(C)(C)OC(=O)N(N)C(C1=C(C(=C(C(=C1)F)F)Cl)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of 3-chloro-2-cyclopropylamino-4,5-difluorobenzoic acid (Example 5d, 2.09 g, 8.45 mmol) in dichloromethane (30 mL) is added tert-butyl carbazate (1.67 g, 12.7 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (2.43 g, 12.7 mmol). After 16 hours, the reaction mixture is diluted with dichloromethane ...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Carbamic ester.Carboxylic acid
Acylhydrazine.Acylhydrazine
null
null
c1ccccc1.C1CC1
HO-
ClCCl
null
16
CC(C)(C)OC(=O)NN.O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1>ClCCl>CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-723272e4c50d4750ba96359bf38303f9
COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)NC(=O)OC(C)(C)C)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cl>>N[C@@H]1CN(c2c(F)cc3c(=O)n(N)c(=O)n(C4CC4)c3c2Cl)C[C@H]1c1ccc(O)cc1
Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1CC(C(C1)C(C)N)(C)C)OC)C1CC1)=O.Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1CC(C(C1)C(C)N)(C)C)OC)C1CC1)=O.C(C)(C)(C)OC(NC(C)C1CN(CC1(C)C)C1=C(C=C2C(N(C(N(C2=C1OC)C1CC1)=O)N)=O)F)=O>>Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H]([C@@H](C1)C1=CC=C(C=C1)O)N)Cl)C1CC1)=O
COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n([CH:26]3[CH2:27][CH2:28]3)c12.CO[c:32]1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3C[CH2:31]3)c21.CO[c:22]1[c:6]([N:5]2[CH2:4][CH:3]([CH:25](C)[NH:2][C:29](OC(C)(C)C)=[O:30])C(C)(C)[CH2:24]2)[c:7]([F:8])[cH:9][c:10]2[c:11](=[O:12])[n:13]([NH2:14])[c:15](=[O:16])[n:1...
COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)NC(=O)OC(C)(C)C)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cl
N[C@@H]1CN(c2c(F)cc3c(=O)n(N)c(=O)n(C4CC4)c3c2Cl)C[C@H]1c1ccc(O)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
1198f7ad564668c686597f068eb2d77a7f802ab881b1a1b5782f67d90e62603c
4aafd3fbdb3033daa035ea8e47db79c24910ad3ef71801528a6032fcf9791bf4
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CC[C@H](c4ccccc4)C3)ccc12
C-O-[c;H0;D3;+0:1](:[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6]:[#7;a:7]:1-[C:8]):[c:9](-[#7:10]1-[C:11]-[CH;D3;+0:12](-[CH;D3;+0:13](-C)-[NH;D2;+0:14]-[C;H0;D3;+0:15](=[O;H0;D1;+0:16])-O-C(-C)(-C)-C)-C(-C)(-C)-[CH2;D2;+0:17]-1):[c:18].C-O-[c;H0;D3;+0:19]1:c(-N2-C-C(-C(-C)-N)-C(-C)(-C)-C-2):c(-F):c:c2:c(=O):n(-N):c(=O):n(-C3-C-[...
null
[]
null
null
null
null
(gggg) 3-Amino-7-[4-(1-aminoethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-1H-quinazoline-2,4-dione hydrochloride (Compound 86) (mp 230° C., MS ES: m/z 406 (MH+)) from {1-[1-(3-amino-1-cyclopropyl-6-fluoro-8-methoxy-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-7-yl)-4,4-dimethylpyrrolidin-3-yl]ethyl}car...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Carbamic ester.Ether.Ether.Ether.Ether.Primary amine.Primary amine.Primary amine.Primary amine.Tertiary amine.Tertiary amine.Boc
Aromatic halide.Aromatic alcohol.Primary amine
C1CCNC1.c1ccc2ncncc2c1.C1CC1.C1CCNC1.c1ccc2ncncc2c1.C1CC1.C1CC[NH]C1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1.c1ccccc1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1.c1ccccc1
HF
null
null
null
COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.COc1c(N2CC(C(C)NC(=O)OC(C)(C)C)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cl>>N[C@@H]1CN(c2c(F)cc3c(=O)n(N)c(=O)n(C4CC4)c3c2Cl)C[C@H]1c1ccc(O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-78d431e5d1344941ac084e1b69f85abf
Cc1c(N2CC3C(C2)C3NC(=O)OC(C)(C)C)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cc1c(N2CC3C(N)C3C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>>Cc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1CC2C(C2C1)N)C)C1CC1)=O.Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1CC2C(C2C1)N)C)C1CC1)=O.C(C)(C)(C)OC(NC1C2CN(CC12)C1=C(C=C2C(N(C(N(C2=C1C)C1CC1)=O)N)=O)F)=O>>Cl.NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1CC(C(C1)C(C)N)(C)C)C)C1CC1)=O
CC(C)(C)OC(=O)[NH:9][CH:7]1[CH:6]2[CH2:5][N:4]([c:3]3[c:2]([CH3:1])[c:28]4[c:17]([cH:16][c:14]3[F:15])[c:18](=[O:19])[n:20]([NH2:21])[c:22](=[O:23])[n:24]4[CH:25]3[CH2:26][CH2:27]3)[CH2:11][CH:10]21.Cc1c(N2CC3[CH:8](N)[CH:12]3[CH2:13]2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH:6]([CH:7]([CH3...
Cc1c(N2CC3C(C2)C3NC(=O)OC(C)(C)C)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cc1c(N2CC3C(N)C3C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
Cc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
0e6ab62436720bc15a1cb658e7094c26f03aa45e11575f623e55e0444c758050
8fe70cbebf6ccf1f29514aa2b36dba78ff5ca891742687bf689e78cf1f7960ba
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[CH;D3;+0:2]1-[C:3]2-[C:4]-[N;H0;D3;+0:5](-[c:6](:[c:7]):[c:8]:[c:9]:[#7;a:10])-[CH2;D2;+0:11]-[CH;D3;+0:12]-2-1.C-c1:c(-N2-C-C3-[CH;D3;+0:13](-[CH2;D2;+0:14]-2)-[CH;D3;+0:15]-3-N):c(-F):c:c2:c(=O):n(-N):c(=O):n(-C3-C-C-3):c:1:2>>[#7;a:10]:[c:9]:[c:8]:[c:6](-[N;H0;D3;+0:5]1-[C:4]-[C:3](...
null
[]
null
null
null
null
(aaaaaa) 3-Amino-7-(6-amino-3-azabicyclo[3.1.0]hex-3-yl)-1-cyclopropyl-6-fluoro-8-methyl-1H-quinazoline-2,4-dione hydrochloride (Compound 134) (mp 180–182° C., MS ES: m/z 346 (MH+)) from [3-(3-amino-1-cyclopropyl-6-fluoro-8-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-azabicyclo[3.1.0]hex-6-yl]carbamic acid te...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ether.Primary amine.Primary amine.Tertiary amine.Tertiary amine.Boc
Primary amine.Tertiary amine
C1[NH]CC2CC12.C1NCC2CC12.c1ccc2ncncc2c1.C1CC1
C1CC[NH]C1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HF
null
null
null
Cc1c(N2CC3C(C2)C3NC(=O)OC(C)(C)C)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.Cc1c(N2CC3C(N)C3C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>>Cc1c(N2CC(C(C)N)C(C)(C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1844604fef6b40a99dc875eff2d94f9d
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1.NCc1ccccc1>>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)F)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O.C(C)N(CC)CC.C(C1=CC=CC=C1)N>>C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)NCC1=CC=CC=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O
F[c:16]1[c:14]([F:15])[c:13]([N:12]2[CH2:11][CH2:10][C@H:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:46]2)[c:44]([F:45])[c:43]2[c:25]1[c:26](=[O:27])[n:28]([NH:29][C:30](=[O:31])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[c:37](=[O:38])[n:39]2[CH:40]1[CH2:41][CH2:42]1.[NH2:17][CH2:18][c:19]1[cH:20][cH:...
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1.NCc1ccccc1
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)cc(NCc3ccccc3)c12
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]:[c:6]2:[#7;a:7](-[C:8]):[c:9]:[#7;a:10](-[#7:11]-[C:12](=[O;D1;H0:13])-[#8:14]-[C:15](-[C;D1;H3:16])(-[C;D1;H3:17])-[C;D1;H3:18]):[c:19](=[O;D1;H0:20]):[c:21]:2:1.[NH2;D1;+0:22]-[C:23]-[c:24]>>[C:8]-[#7;a:7]1:[c:9]:[#7;a:10](-[#7:11]-[C:12](=[O;D1;H0:13])-[#8:14]-[C:15]...
86.8
[{"value": 86.8, "product": "C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)NCC1=CC=CC=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of {7-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-1-cyclopropyl-1,4-dihydro-2,4-dioxo-5,6,8-trifluoro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 8 (0.51 g, 0.914 mmol), triethylamine (1.3 mL, 9.3 mmol), and benzylamine (0.50 mL, 4.6 mmol) in dimethyl sulfoxide (7.5 mL) is heated at ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
C1CC[NH]C1.c1ccccc1.c1ccc2ncncc2c1.C1CC1
HF
CS(=O)C
null
null
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(F)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1.NCc1ccccc1>CS(=O)C>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-47358ccb45f14dbb802e1a7480724754
CI.CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1>>CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(N(C)C(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1
IC.C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H](CC1)N(C)C(=O)OC(C)(C)C)Cl)C1CC1)=O)=O.[H-].[Na+]>>C(C)(C)(C)OC(N(C)N1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H](CC1)N(C)C(=O)OC(C)(C)C)Cl)C1CC1)=O)=O
I[CH3:23].[CH3:1][N:2]([C:3](=[O:4])[O:5][C:6]([CH3:7])([CH3:8])[CH3:9])[C@H:10]1[CH2:11][CH2:12][N:13]([c:14]2[c:15]([F:16])[cH:17][c:18]3[c:19](=[O:20])[n:21]([NH:22][C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[c:31](=[O:32])[n:33]([CH:34]4[CH2:35][CH2:36]4)[c:37]3[c:38]2[Cl:39])[CH2:40]1>>[CH3:1][N:2]([C...
CI.CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1
CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(N(C)C(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1
null
null
CN(C=O)C.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
29c841ae076cb6ee785aad2a4e3ce1a9b47357d7ad25657b8d9991b1347f5721
c485eddcb40c5a0d396ffdb624041effa09ee4f5ca2ecce3fe13077cf65004ed
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
I-[CH3;D1;+0:1].[#7;a:2]:[c:3]:[#7;a:4](-[NH;D2;+0:5]-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12]):[c:13]>>[#7;a:2]:[c:3]:[#7;a:4](-[N;H0;D3;+0:5](-[CH3;D1;+0:1])-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12]):[c:13]
48.2
[{"value": 48.2, "product": "C(C)(C)(C)OC(N(C)N1C(N(C2=C(C(=C(C=C2C1=O)F)N1C[C@H](CC1)N(C)C(=O)OC(C)(C)C)Cl)C1CC1)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of {7-[(S)-3-(tert-butoxycarbonyl-N-methylamino)-pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 8 (0.238 g, 0.421 mmol) in N,N-dimethylformamide (5 mL) at −78° C. under nitrogen atmosphere is added sodium hydride (60% d...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester
Carbamic ester
null
null
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HI
CN(C=O)C.C(C)(=O)OCC
null
0.5
CI.CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1>CN(C=O)C.C(C)(=O)OCC>CN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cc3c(=O)n(N(C)C(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2Cl)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c978877a17c84bafbb196b62c0e17983
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1>>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(N)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)NCC1=CC=CC=C1)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O>>C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)N)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O
c1ccc(C[NH:17][c:16]2[c:14]([F:15])[c:13]([N:12]3[CH2:11][CH2:10][C@H:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:39]3)[c:37]([F:38])[c:36]3[c:18]2[c:19](=[O:20])[n:21]([NH:22][C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[c:30](=[O:31])[n:32]3[CH:33]2[CH2:34][CH2:35]2)cc1>>[CH3:1][C:2]([CH...
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(N)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
null
[OH-].[OH-].[Pd+2]
O1CCCC1
Deprotection
OtherReaction
93c46c2f9981b731115295839d7158a8a73faedd00707b7604ace2fa5f580cbc
f6571fb5b7780a2b467937abfba91ba7d787f19d503265f299ff4a25a08963bd
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
[#7;a:1]:[c:2]:[c:3](:[c:4]:[#7;a:5]):[c:6](-[NH;D2;+0:7]-C-c1:c:c:c:c:c:1):[c:8]>>[#7;a:1]:[c:2]:[c:3](:[c:4]:[#7;a:5]):[c:6](-[NH2;D1;+0:7]):[c:8]
76
[{"value": 76.0, "product": "C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C(=C2C1=O)N)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)F)C1CC1)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
{7-[(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-benzylamino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-2,4-dioxo-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 10 (0.435 g, 0.676 mmol) in tetrahydrofuran (20 mL) is hydrogenated at room temperature and atmospheric pressure over 20% palladium hydroxide...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Primary amine
c1ccccc1
null
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
Other
[OH-].[OH-].[Pd+2].O1CCCC1
null
null
CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(NCc3ccccc3)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1>[OH-].[OH-].[Pd+2].O1CCCC1>CC(C)(C)OC(=O)N[C@H]1CCN(c2c(F)c(N)c3c(=O)n(NC(=O)OC(C)(C)C)c(=O)n(C4CC4)c3c2F)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c2d5044022f14e53baf14d00dca00803
CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl>>CC(C)(C)OC(=O)Nn1c(=O)c2cc(F)c(F)c(Cl)c2n(C2CC2)c1=O
C(C)(C)(C)OC(=O)N(N)C(C1=C(C(=C(C(=C1)F)F)Cl)NC1CC1)=O.C([O-])([O-])=O.[K+].[K+].ClC(Cl)(OC(OC(Cl)(Cl)Cl)=O)Cl.O1CCCC1>>C(C)(C)(C)OC(NN1C(N(C2=C(C(=C(C=C2C1=O)F)F)Cl)C1CC1)=O)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:9]([NH2:8])[C:10](=[O:11])[c:12]1[cH:13][c:14]([F:15])[c:16]([F:17])[c:18]([Cl:19])[c:20]1[NH:21][CH:22]1[CH2:23][CH2:24]1.ClC(Cl)(Cl)O[C:25](OC(Cl)(Cl)Cl)=[O:26]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][n:9]1[c:10](=[O:11])[c:12]2[cH:13][c:14]([F:15])[c...
CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
CC(C)(C)OC(=O)Nn1c(=O)c2cc(F)c(F)c(Cl)c2n(C2CC2)c1=O
null
null
C(C)(=O)OCC
Aromatic Heterocycle Formation
OtherReaction
c6b4d02c6c0bff2689f07d1c645d1cae1ec2640b111b023685404790b9cae33b
4cbf753e6b20db27fb12d18a32e4abed7429535b4341cc531aae4e1f32e2aca8
O=c1[nH]c(=O)n(C2CC2)c2ccccc12
Cl-C(-Cl)(-Cl)-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-O-C(-Cl)(-Cl)-Cl.[C;D1;H3:3]-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[#8:7]-[C;H0;D3;+0:8](=[O;D1;H0:9])-[N;H0;D3;+0:10](-[NH2;D1;+0:11])-[C;H0;D3;+0:12](=[O;D1;H0:13])-[c:14](:[c:15]):[c:16](-[NH;D2;+0:17]-[C:18]1-[C:19]-[C:20]-1):[c:21]>>[C;D1;H3:3]-[C:4](-[C;D1;H3:5])(-[C;D1;H...
null
[]
null
null
null
null
To a solution of (3-chloro-2-cyclopropylamino-4,5-difluorobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (Example 6c) (1.93 g, 5.34 mmol) in tetrahydrofuran (50 mL) is added potassium carbonate (3.69 g, 26.7 mol) and triphosgene (2.06 g, 6.95 mmol). The reaction mixture is refluxed for 90 minutes, cooled to room te...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Acylhydrazine.Trichloro group.Trichloro group.Carbamic ester.Carbonic Ester.Ether.Secondary amine.Boc
Carbamic ester.Ether.Boc
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC1
HCl
C(C)(=O)OCC
null
null
CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl>C(C)(=O)OCC>CC(C)(C)OC(=O)Nn1c(=O)c2cc(F)c(F)c(Cl)c2n(C2CC2)c1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7f92a3d7fb874808929e1d951998575f
NN(Cc1ccccc1)Cc1ccccc1.Nc1cc(F)c(F)cc1C(=O)O>>Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1
FC=1C=C(C(C(=O)O)=CC1F)N.C(C1=CC=CC=C1)N(N)CC1=CC=CC=C1.Cl.C(C)N=C=NCCCN(C)C>>C(C1=CC=CC=C1)N(NC(C1=C(C=C(C(=C1)F)F)N)=O)CC1=CC=CC=C1
[NH2:12][N:13]([CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1)[CH2:21][c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1.O[C:10]([c:9]1[c:2]([NH2:1])[cH:3][c:4]([F:5])[c:6]([F:7])[cH:8]1)=[O:11]>>[NH2:1][c:2]1[cH:3][c:4]([F:5])[c:6]([F:7])[cH:8][c:9]1[C:10](=[O:11])[NH:12][N:13]([CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19...
NN(Cc1ccccc1)Cc1ccccc1.Nc1cc(F)c(F)cc1C(=O)O
Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1
null
null
C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
87776deec7c8d787307af11af64c4c1226af5b5e46e4fe8124762f384e2eebf3
82203b4f77b2f7d17908f28dcc1ecc7f616d152f963b273ffea1254f61a0fe2d
O=C(NN(Cc1ccccc1)Cc1ccccc1)c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#7:7](-[C:8])-[NH2;D1;+0:9]>>[C:6]-[#7:7](-[C:8])-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
157.5
[{"value": 157.5, "product": "C(C1=CC=CC=C1)N(NC(C1=C(C=C(C(=C1)F)F)N)=O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
25
CELSIUS
18
HOUR
4,5-Difluoroanthranilic acid (4.73 g, 27.3 mmol) and N,N-dibenzylhydrazine (8.69 g, 42 mmol) are combined in 200 mL of methylene chloride. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC) (7.85 g, 41 mmol) is then added to this solution, and the mixture is stirred for 18 hours at 25° C., The solution ...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Carboxylic acid
Acylhydrazine
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HO-
C(Cl)Cl
25
18
NN(Cc1ccccc1)Cc1ccccc1.Nc1cc(F)c(F)cc1C(=O)O>C(Cl)Cl>Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-80072c018d95452cb4a32b07e670454c
Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl>>O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
C(C1=CC=CC=C1)N(NC(C1=C(C=C(C(=C1)F)F)N)=O)CC1=CC=CC=C1.ClC(Cl)(OC(OC(Cl)(Cl)Cl)=O)Cl.C(=O)(O)[O-].[Na+]>>C(C1=CC=CC=C1)N(N1C(NC2=CC(=C(C=C2C1=O)F)F)=O)CC1=CC=CC=C1
[NH2:3][c:4]1[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10][c:11]1[C:12](=[O:13])[NH:14][N:15]([CH2:16][c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22]1)[CH2:23][c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1.ClC(Cl)(Cl)O[C:2](OC(Cl)(Cl)Cl)=[O:1]>>[O:1]=[c:2]1[nH:3][c:4]2[cH:5][c:6]([F:7])[c:8]([F:9])[cH:10][c:11]2[c:12](=[O:13])[n:14]1[...
Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
null
null
C(Cl)Cl
Aromatic Heterocycle Formation
OtherReaction
3088685657879b5d46a8d3bdf91412bc59e92855b7b82124def1c1f5ec65dff3
cbc1e68b05ec8e5493d5786cee084ad7a55547a0f4620c6ee39c1ab17c8df5ac
O=c1[nH]c2ccccc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
Cl-C(-Cl)(-Cl)-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-O-C(-Cl)(-Cl)-Cl.[C:3]-[#7:4](-[C:5])-[NH;D2;+0:6]-[C;H0;D3;+0:7](=[O;D1;H0:8])-[c:9](:[c:10]):[c:11](-[NH2;D1;+0:12]):[c:13]>>[C:3]-[#7:4](-[C:5])-[n;H0;D3;+0:6]1:[c;H0;D3;+0:7](=[O;D1;H0:8]):[c:9](:[c:10]):[c:11](:[c:13]):[nH;D2;+0:12]:[c;H0;D3;+0:1]:1=[O;D1;H0:2]
198.7
[{"value": 198.7, "product": "C(C1=CC=CC=C1)N(N1C(NC2=CC(=C(C=C2C1=O)F)F)=O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
25
CELSIUS
20
HOUR
2-Amino-4,5-difluorobenzoic acid, 2,2-dibenzylhydrazide (Example 15) (0.81 g, 2.2 mmol) and triphosgene (0.33 g, 1.1 mmol) are combined in 100 mL of methylene chloride and stirred at 25° C. for 20 hours. The solution is poured into 200 mL of saturated NaHCO3, the layers are separated, and the aqueous layer is washed th...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Trichloro group.Trichloro group.Carbonic Ester.Primary amine
null
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
25
20
Nc1cc(F)c(F)cc1C(=O)NN(Cc1ccccc1)Cc1ccccc1.O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl>C(Cl)Cl>O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-daaaaa8f0d4e49baa153f8600eb11663
BrCC1CC1.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1>>O=c1c2cc(F)c(F)cc2n(CC2CC2)c(=O)n1N(Cc1ccccc1)Cc1ccccc1
C(C1=CC=CC=C1)N(N1C(NC2=CC(=C(C=C2C1=O)F)F)=O)CC1=CC=CC=C1.[H-].[Na+].BrCC1CC1>>C(C1=CC=CC=C1)N(N1C(N(C2=CC(=C(C=C2C1=O)F)F)CC1CC1)=O)CC1=CC=CC=C1
Br[CH2:12][CH:13]1[CH2:14][CH2:15]1.[O:1]=[c:2]1[c:3]2[cH:4][c:5]([F:6])[c:7]([F:8])[cH:9][c:10]2[nH:11][c:16](=[O:17])[n:18]1[N:19]([CH2:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1)[CH2:27][c:28]1[cH:29][cH:30][cH:31][cH:32][cH:33]1>>[O:1]=[c:2]1[c:3]2[cH:4][c:5]([F:6])[c:7]([F:8])[cH:9][c:10]2[n:11]([CH2:12][CH:13...
BrCC1CC1.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
O=c1c2cc(F)c(F)cc2n(CC2CC2)c(=O)n1N(Cc1ccccc1)Cc1ccccc1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0b0179903a04a1706fdb5bd83526eacf6acd2b47a87012dec86fcbe52dd05a28
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
O=c1c2ccccc2n(CC2CC2)c(=O)n1N(Cc1ccccc1)Cc1ccccc1
Br-[CH2;D2;+0:1]-[C:2]1-[C:3]-[C:4]-1.[#7:5]-[#7;a:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[nH;D2;+0:11]:[c:12]:1=[O;D1;H0:13]>>[#7:5]-[#7;a:6]1:[c:7]:[c:8]:[c:9](:[c:10]):[n;H0;D3;+0:11](-[CH2;D2;+0:1]-[C:2]2-[C:3]-[C:4]-2):[c:12]:1=[O;D1;H0:13]
67
[{"value": 67.0, "product": "C(C1=CC=CC=C1)N(N1C(N(C2=CC(=C(C=C2C1=O)F)F)CC1CC1)=O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 3-dibenzylamino-6,7-difluoro-1H-quinazoline-2,4-dione (Example 16) (0.43 g, 1.1 mmol) in 10 mL of N,N-dimethylformamide is added to a suspension of sodium hydride (0.05 g, 1.3 mmol) in 10 mL of N,N-dimethylformamide and stirred for 30 minutes. Bromomethylcyclopropane (0.16 mL, 1.6 mmol) is added, and the ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC1.c1ccccc1.c1ccccc1
HBr
CN(C=O)C
null
0.5
BrCC1CC1.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1>CN(C=O)C>O=c1c2cc(F)c(F)cc2n(CC2CC2)c(=O)n1N(Cc1ccccc1)Cc1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-de33f49a4f9a4548b0cd9c65b986092f
CCI.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1>>CCn1c(=O)n(N(Cc2ccccc2)Cc2ccccc2)c(=O)c2cc(F)c(F)cc21
C(C1=CC=CC=C1)N(N1C(NC2=CC(=C(C=C2C1=O)F)F)=O)CC1=CC=CC=C1.[H-].[Na+].C(C)I>>C(C1=CC=CC=C1)N(N1C(N(C2=CC(=C(C=C2C1=O)F)F)CC)=O)CC1=CC=CC=C1
I[CH2:2][CH3:1].[nH:3]1[c:4](=[O:5])[n:6]([N:7]([CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[CH2:15][c:16]2[cH:17][cH:18][cH:19][cH:20][cH:21]2)[c:22](=[O:23])[c:24]2[cH:25][c:26]([F:27])[c:28]([F:29])[cH:30][c:31]12>>[CH3:1][CH2:2][n:3]1[c:4](=[O:5])[n:6]([N:7]([CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[...
CCI.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
CCn1c(=O)n(N(Cc2ccccc2)Cc2ccccc2)c(=O)c2cc(F)c(F)cc21
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0b0179903a04a1706fdb5bd83526eacf6acd2b47a87012dec86fcbe52dd05a28
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
O=c1[nH]c2ccccc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[#7:3]-[#7;a:4]1:[c:5]:[c:6]:[c:7](:[c:8]):[nH;D2;+0:9]:[c:10]:1=[O;D1;H0:11]>>[#7:3]-[#7;a:4]1:[c:5]:[c:6]:[c:7](:[c:8]):[n;H0;D3;+0:9](-[CH2;D2;+0:1]-[C;D1;H3:2]):[c:10]:1=[O;D1;H0:11]
73.3
[{"value": 73.3, "product": "C(C1=CC=CC=C1)N(N1C(N(C2=CC(=C(C=C2C1=O)F)F)CC)=O)CC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 3-dibenzylamino-6,7-difluoro-1H-quinazoline-2,4-dione (Example 16) (0.43 g, 1.1 mmol) in 10 mL of N,N-dimethylformamide is added to a suspension of sodium hydride (0.05 g, 1.3 mmol) in 10 mL of N,N-dimethylformamide and stirred for 30 minutes. Ethyl iodide (0.13 mL, 1.6 mmol) is added, and the mixture is ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccccc1.c1ccc2ncncc2c1
HI
CN(C=O)C
null
0.5
CCI.O=c1[nH]c2cc(F)c(F)cc2c(=O)n1N(Cc1ccccc1)Cc1ccccc1>CN(C=O)C>CCn1c(=O)n(N(Cc2ccccc2)Cc2ccccc2)c(=O)c2cc(F)c(F)cc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-39a15fbd48b4456ab2e1fe32e0c4c74b
CC(C)(C)OC(=O)N(N)C(=O)c1ccccc1.O=C1CCC(=O)N1Cl>>CC(C)(C)OC(=O)N(NCl)C(=O)c1ccccc1
C(C)(C)(C)OC(=O)N(N)C(C1=CC=CC=C1)=O.ClN1C(CCC1=O)=O>>C(C)(C)(C)OC(=O)N(NCl)C(C1=CC=CC=C1)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([NH2:9])[C:11](=[O:12])[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1.O=C1CCC(=O)N1[Cl:10]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([NH:9][Cl:10])[C:11](=[O:12])[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1
CC(C)(C)OC(=O)N(N)C(=O)c1ccccc1.O=C1CCC(=O)N1Cl
CC(C)(C)OC(=O)N(NCl)C(=O)c1ccccc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Functional Group Interconversion
OtherReaction
5c1e0d52d03addd6eb6b1f4214099582787eed3578962faa0a1bba16dd9974fa
d6d9ae1904f6b2a8c6a1e2beda49b48f0e576035412716ace5f37cb3b01d1d12
c1ccccc1
O=C1-C-C-C(=O)-N-1-[Cl;H0;D1;+0:1].[C;D1;H3:2]-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[#8:6]-[C:7](=[O;D1;H0:8])-[#7:9](-[NH2;D1;+0:10])-[C:11](=[O;D1;H0:12])-[c:13]>>[C;D1;H3:2]-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[#8:6]-[C:7](=[O;D1;H0:8])-[#7:9](-[NH;D2;+0:10]-[Cl;H0;D1;+0:1])-[C:11](=[O;D1;H0:12])-[c:13]
null
[]
null
null
1
HOUR
To a solution of a benzoylhydrazinecarboxylic acid tert-butyl ester (Example 7) in acetic acid (5 mL) is added N-chlorosuccinimide (1.2 eq.). After 1 hour, the reaction mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4 and filtered. The filtr...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Acylhydrazine.Tertiary amide.Tertiary amide
Acylhydrazine.Acylhydrazine
C1CCNC1
null
c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
null
1
CC(C)(C)OC(=O)N(N)C(=O)c1ccccc1.O=C1CCC(=O)N1Cl>C(C)(=O)O.C(C)(=O)OCC>CC(C)(C)OC(=O)N(NCl)C(=O)c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cce603932cca4abba7de902112a6eb98
CC(C)(C)OCl.Nc1cc(F)c(F)cc1C(=O)O>>Nc1c(C(=O)O)cc(F)c(F)c1Cl
FC=1C=C(C(C(=O)O)=CC1F)N.C(C)(=O)O.C(C)(C)(C)OCl>>ClC1=C(C(C(=O)O)=CC(=C1F)F)N
CC(C)(C)O[Cl:13].[NH2:1][c:2]1[c:3]([C:4](=[O:5])[OH:6])[cH:7][c:8]([F:9])[c:10]([F:11])[cH:12]1>>[NH2:1][c:2]1[c:3]([C:4](=[O:5])[OH:6])[cH:7][c:8]([F:9])[c:10]([F:11])[c:12]1[Cl:13]
CC(C)(C)OCl.Nc1cc(F)c(F)cc1C(=O)O
Nc1c(C(=O)O)cc(F)c(F)c1Cl
null
null
ClCCl.C(C)(=O)OCC
Functional Group Interconversion
Chlorination
f6effe61353895b318215d8bd9b6bb1105cafbf7be8c217d748df587260b32c3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccccc1
C-C(-C)(-C)-O-[Cl;H0;D1;+0:1].[F;D1;H0:2]-[c:3](:[c:4]):[cH;D2;+0:5]:[c:6](-[N;D1;H2:7]):[c:8]-[C:9](=[O;D1;H0:10])-[O;D1;H1:11]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:5](:[c:3](-[F;D1;H0:2]):[c:4]):[c:6](-[N;D1;H2:7]):[c:8]-[C:9](=[O;D1;H0:10])-[O;D1;H1:11]
100.8
[{"value": 100.8, "product": "ClC1=C(C(C(=O)O)=CC(=C1F)F)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of 4,5-difluoroanthranilic acid (2.45 g, 14.2 mmol) in dichloromethane (25 mL) is added acetic acid (10 mL) and hypochlorous acid tert-butyl ester (1.75 mL, 15.6 mmol). After 2 hours, the reaction mixture is diluted with ethyl acetate and washed with water and brine. The organic layer is dried over MgSO4,...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccccc1
c1ccccc1
c1ccccc1
HO-
ClCCl.C(C)(=O)OCC
null
2
CC(C)(C)OCl.Nc1cc(F)c(F)cc1C(=O)O>ClCCl.C(C)(=O)OCC>Nc1c(C(=O)O)cc(F)c(F)c1Cl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fa7df086e4e6499c96d448bcfa269c2e
CC(C)(C)OCl.Nc1cc(F)ccc1C(=O)O>>Nc1cc(F)c(Cl)cc1C(=O)O
FC=1C=C(C(C(=O)O)=CC1)N.ClOC(C)(C)C>>ClC1=C(C=C(C(C(=O)O)=C1)N)F
CC(C)(C)O[Cl:7].[NH2:1][c:2]1[cH:3][c:4]([F:5])[cH:6][cH:8][c:9]1[C:10](=[O:11])[OH:12]>>[NH2:1][c:2]1[cH:3][c:4]([F:5])[c:6]([Cl:7])[cH:8][c:9]1[C:10](=[O:11])[OH:12]
CC(C)(C)OCl.Nc1cc(F)ccc1C(=O)O
Nc1cc(F)c(Cl)cc1C(=O)O
null
null
ClCCl.C(C)(=O)O.C(Cl)Cl
Functional Group Interconversion
Chlorination
f6effe61353895b318215d8bd9b6bb1105cafbf7be8c217d748df587260b32c3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccccc1
C-C(-C)(-C)-O-[Cl;H0;D1;+0:1].[F;D1;H0:2]-[c:3](:[c:4]):[cH;D2;+0:5]:[c:6]:[c:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:5](:[c:6]:[c:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]):[c:3](-[F;D1;H0:2]):[c:4]
111.2
[{"value": 111.2, "product": "ClC1=C(C=C(C(C(=O)O)=C1)N)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
90
MINUTE
To a solution of 4-fluoroanthranilic acid (0.882 g, 5.69 mmol) in methylene chloride (50 ML) and acetic acid (10 mL) is added tert-butyl hypochlorite (0.71 mL, 6.25 mmol) solution in dichloromethane (1 mL) dropwise over 1 minute. After 90 minutes, the reaction mixture is washed with water and brine. The organic layer i...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccccc1
c1ccccc1
c1ccccc1
HO-
ClCCl.C(C)(=O)O.C(Cl)Cl
null
1.5
CC(C)(C)OCl.Nc1cc(F)ccc1C(=O)O>ClCCl.C(C)(=O)O.C(Cl)Cl>Nc1cc(F)c(Cl)cc1C(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-af712a0070fe42688003d15eb8dd1bab
CO.O=C(O)c1cc(F)c(F)cc1NC1CC1>>COC(=O)c1cc(F)c(F)cc1NC1CC1
C1(CC1)NC1=C(C(=O)O)C=C(C(=C1)F)F.ClCCl.CO.C[Si](C)(C)C=[N+]=[N-]>>COC(C1=C(C=C(C(=C1)F)F)NC1CC1)=O
[CH3:1][OH:2].O[C:3](=[O:4])[c:5]1[cH:6][c:7]([F:8])[c:9]([F:10])[cH:11][c:12]1[NH:13][CH:14]1[CH2:15][CH2:16]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([F:8])[c:9]([F:10])[cH:11][c:12]1[NH:13][CH:14]1[CH2:15][CH2:16]1
CO.O=C(O)c1cc(F)c(F)cc1NC1CC1
COC(=O)c1cc(F)c(F)cc1NC1CC1
null
null
O.C(=O)O
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccc(NC2CC2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[OH;D1;+0:7]>>[C;D1;H3:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
null
[]
null
null
0.5
HOUR
To a solution of 2-cyclopropylamino-4,5-difluorobenzoic acid (Example 5a) (6.0 g, 28.1 mmol), dichloromethane (100 mL), and methanol (20 mL) is added (trimethylsilyl)diazomethane (2.9 M solution in hexane) dropwise until the evolution of gas stops. The solution is stirred at room temperature for 0.5 hour and 88% formic...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1.C1CC1
HO-
O.C(=O)O
null
0.5
CO.O=C(O)c1cc(F)c(F)cc1NC1CC1>O.C(=O)O>COC(=O)c1cc(F)c(F)cc1NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-bf2e5b26c85a4325b8e0f4a034dc0c42
CCOC(=O)c1cc(F)c(F)cc1NC1CC1.O=C=NSCl>>O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12
C(C)OC(C1=C(C=C(C(=C1)F)F)NC1CC1)=O.ClSN=C=O>>C1(CC1)N1C(NC(C2=CC(=C(C=C12)F)F)=O)=O
CCO[C:2](=[O:1])[c:17]1[c:10]([NH:6][CH:7]2[CH2:8][CH2:9]2)[cH:11][c:12]([F:13])[c:14]([F:15])[cH:16]1.ClS[N:3]=[C:4]=[O:5]>>[O:1]=[c:2]1[nH:3][c:4](=[O:5])[n:6]([CH:7]2[CH2:8][CH2:9]2)[c:10]2[cH:11][c:12]([F:13])[c:14]([F:15])[cH:16][c:17]12
CCOC(=O)c1cc(F)c(F)cc1NC1CC1.O=C=NSCl
O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12
null
null
ClCCl
Aromatic Heterocycle Formation
OtherReaction
121620ba7556cb3be25b0e31bbbe99959c37e6879059ed5927290eacc9f43c1e
3513c98a3be17756938dbfa89da7e867549065d9a015fcc025e780b6be802c11
O=c1[nH]c(=O)n(C2CC2)c2ccccc12
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[NH;D2;+0:6]-[C:7]1-[C:8]-[C:9]-1):[c:10].Cl-S-[N;H0;D2;+0:11]=[C;H0;D2;+0:12]=[O;D1;H0:13]>>[O;D1;H0:2]=[c;H0;D3;+0:1]1:[nH;D2;+0:11]:[c;H0;D3;+0:12](=[O;D1;H0:13]):[n;H0;D3;+0:6](-[C:7]2-[C:8]-[C:9]-2):[c:5](:[c:10]):[c:3]:1:[c:4]
38.2
[{"value": 38.2, "product": "C1(CC1)N1C(NC(C2=CC(=C(C=C12)F)F)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-20
CELSIUS
null
null
To a solution of 2-cyclopropylamino-4,5-difluorobenzoic acid ethyl ester (Example 22) (5.0 g, 22.0 mmol) in dry dichloromethane (120 mL) under a N2 atmosphere is added chlorosulfanyl isocyanate (3.11 g, 22 mmol). The solution is reacted at room temperature for 4 hours, and the solvent is removed under reduced pressure....
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine.Monosulfide
null
c1ccccc1
c1ccc2ncncc2c1
C1CC1.c1ccc2ncncc2c1
HCl
ClCCl
-20
null
CCOC(=O)c1cc(F)c(F)cc1NC1CC1.O=C=NSCl>ClCCl>O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fa49a4c2dd0b4b8eb96227f4cd80fd12
COc1c(F)c(F)cc(C(=O)NC(=O)NC2CC2)c1F>>COc1c(F)c(F)cc2c(=O)[nH]c(=O)n(C3CC3)c12
[NH4+].[Cl-].C1(CC1)NC(=O)NC(C1=C(C(=C(C(=C1)F)F)OC)F)=O.[H-].[Na+]>>C1(CC1)N1C(NC(C2=CC(=C(C(=C12)OC)F)F)=O)=O
F[c:19]1[c:3]([O:2][CH3:1])[c:4]([F:5])[c:6]([F:7])[cH:8][c:9]1[C:10](=[O:11])[NH:12][C:13](=[O:14])[NH:15][CH:16]1[CH2:17][CH2:18]1>>[CH3:1][O:2][c:3]1[c:4]([F:5])[c:6]([F:7])[cH:8][c:9]2[c:10](=[O:11])[nH:12][c:13](=[O:14])[n:15]([CH:16]3[CH2:17][CH2:18]3)[c:19]12
COc1c(F)c(F)cc(C(=O)NC(=O)NC2CC2)c1F
COc1c(F)c(F)cc2c(=O)[nH]c(=O)n(C3CC3)c12
null
null
CN(C=O)C.O1CCCC1
Aromatic Heterocycle Formation
OtherReaction
6e75d4eb6a84e483e2ddadbb951c8da924a964b9531d8911fcf248fc4015db7e
bb4080cca4c6d1e1f6fb16e2d4c2c839a823abdb78eb7b61ba313755abab2570
O=c1[nH]c(=O)n(C2CC2)c2ccccc12
F-[c;H0;D3;+0:1](:[c:2](-[#8:3]):[c:4]):[c:5](-[C;H0;D3;+0:6](=[O;D1;H0:7])-[NH;D2;+0:8]-[C;H0;D3;+0:9](=[O;D1;H0:10])-[NH;D2;+0:11]-[C:12]1-[C:13]-[C:14]-1):[c:15]>>[#8:3]-[c:2](:[c:4]):[c;H0;D3;+0:1]1:[c:5](:[c:15]):[c;H0;D3;+0:6](=[O;D1;H0:7]):[nH;D2;+0:8]:[c;H0;D3;+0:9](=[O;D1;H0:10]):[n;H0;D3;+0:11]:1-[C:12]1-[C:1...
null
[]
null
null
null
null
A solution of 1-cyclopropyl-3-(3-methoxy-2,4,5-trifluorobenzoyl)urea (Example 27b, 0.94 g, 3.26 mmol) in tetrahydrofuran (20 mL) and N,N-dimethylformamide (5 mL) is treated with sodium hydride (0.275 g, 6.8 mmol, 60% in mineral oil dispersion) and heated at reflux for 16 hours. The mixture is cooled, treated with satur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Urea.Unsubstituted dicarboximide
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1.C1CC1
HF
CN(C=O)C.O1CCCC1
null
null
COc1c(F)c(F)cc(C(=O)NC(=O)NC2CC2)c1F>CN(C=O)C.O1CCCC1>COc1c(F)c(F)cc2c(=O)[nH]c(=O)n(C3CC3)c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9609d165691a467a99ceed9a09f8958b
COC(=O)c1cc(F)c(F)c2c1NC(C)CO2.O=C=NS(=O)(=O)Cl>>CC1COc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
COC(=O)C=1C=C(C(=C2C1NC(CO2)C)F)F.ClS(=O)(=O)N=C=O.C(C)N(CC)CC>>FC=1C=C2C(NC(N3C(COC(C1F)=C32)C)=O)=O
CO[C:12]([c:11]1[cH:10][c:8]([F:9])[c:6]([F:7])[c:5]2[c:18]1[NH:17][CH:2]([CH3:1])[CH2:3][O:4]2)=[O:13].O=S(=O)(Cl)[N:14]=[C:15]=[O:16]>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([F:7])[c:8]([F:9])[cH:10][c:11]3[c:12](=[O:13])[nH:14][c:15](=[O:16])[n:17]1[c:18]23
COC(=O)c1cc(F)c(F)c2c1NC(C)CO2.O=C=NS(=O)(=O)Cl
CC1COc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
null
null
ClCCl
Aromatic Heterocycle Formation
OtherReaction
91ec8e3defb45cffcf889ff90e1ccb2a57c84d5e3659baecbf62a17c20847a03
b2e640ad6adb277738cae8a944067d998d1107d1f884bf69b59d55eb50b99f16
O=c1[nH]c(=O)n2c3c(cccc13)OCC2
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]1:[c:6]-[#8:7]-[C:8]-[C:9](-[C;D1;H3:10])-[NH;D2;+0:11]-1.Cl-S(=O)(=O)-[N;H0;D2;+0:12]=[C;H0;D2;+0:13]=[O;D1;H0:14]>>[C;D1;H3:10]-[C:9]1-[C:8]-[#8:7]-[c:6]:[c:5]2:[c:3](:[c:4]):[c;H0;D3;+0:1](=[O;D1;H0:2]):[nH;D2;+0:12]:[c;H0;D3;+0:13](=[O;D1;H0:14]):[n;H0;D3;+0:11]:2...
15.9
[{"value": 15.9, "product": "FC=1C=C2C(NC(N3C(COC(C1F)=C32)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A solution of 1.5 g (6.2 mmol) of 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester (Example 32a) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.92 g (6.5 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at room temperature for 18 hours and the ...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
null
c1ccc2c(c1)NCCO2
c1cc2c3c(cncn3[CH]CO2)c1
c1cc2c3c(cncn3[CH]CO2)c1
HCl
ClCCl
null
18
COC(=O)c1cc(F)c(F)c2c1NC(C)CO2.O=C=NS(=O)(=O)Cl>ClCCl>CC1COc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-52f47f320e094ba2afae0887085e38a9
COC(=O)c1cc(F)c(F)c2c1NC(C)CC2.O=C=NS(=O)(=O)Cl>>CC1CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
COC(=O)C=1C=C(C(=C2CCC(NC12)C)F)F.ClS(=O)(=O)N=C=O.C(C)(=O)[O-].[Na+].CC(C)([O-])C.[Na+]>>FC1=C(C=C2C(NC(N3C2=C1CCC3C)=O)=O)F
CO[C:12]([c:11]1[cH:10][c:8]([F:9])[c:6]([F:7])[c:5]2[c:18]1[NH:17][CH:2]([CH3:1])[CH2:3][CH2:4]2)=[O:13].O=S(=O)(Cl)[N:14]=[C:15]=[O:16]>>[CH3:1][CH:2]1[CH2:3][CH2:4][c:5]2[c:6]([F:7])[c:8]([F:9])[cH:10][c:11]3[c:12](=[O:13])[nH:14][c:15](=[O:16])[n:17]1[c:18]23
COC(=O)c1cc(F)c(F)c2c1NC(C)CC2.O=C=NS(=O)(=O)Cl
CC1CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
null
null
ClCCl
Aromatic Heterocycle Formation
OtherReaction
5bd582ecfe6bc34a51834b8f636a21d51ead25d0f8a0211e2b466981179d44dc
b2e640ad6adb277738cae8a944067d998d1107d1f884bf69b59d55eb50b99f16
O=c1[nH]c(=O)n2c3c(cccc13)CCC2
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](:[c:6])-[NH;D2;+0:7]-[C:8](-[C;D1;H3:9])-[C:10].Cl-S(=O)(=O)-[N;H0;D2;+0:11]=[C;H0;D2;+0:12]=[O;D1;H0:13]>>[C:10]-[C:8](-[C;D1;H3:9])-[n;H0;D3;+0:7]1:[c:5](:[c:6]):[c:3](:[c:4]):[c;H0;D3;+0:1](=[O;D1;H0:2]):[nH;D2;+0:11]:[c;H0;D3;+0:12]:1=[O;D1;H0:13]
72.1
[{"value": 72.1, "product": "FC1=C(C=C2C(NC(N3C2=C1CCC3C)=O)=O)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-20
CELSIUS
1
HOUR
A solution of 1.07 g (4.4 mmol) of 5,6-difluoro-2-methyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (Example 32) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.85 g (6.0 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 1 hour, treated with 1.0 g (...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
null
c1ccc2c(c1)CCCN2
c1cc2c3c(cncn3[CH]CC2)c1
c1cc2c3c(cncn3[CH]CC2)c1
HCl
ClCCl
-20
1
COC(=O)c1cc(F)c(F)c2c1NC(C)CC2.O=C=NS(=O)(=O)Cl>ClCCl>CC1CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-296269dc43554704b3f2db025bb12e66
CCOC(=O)c1cc(F)c(SC)nc1NC1CC1.O=C=NS(=O)(=O)Cl>>CSc1nc2c(cc1F)c(=O)[nH]c(=O)n2C1CC1
CC(C)([O-])C.[Na+].ClS(=O)(=O)N=C=O.C(C)(=O)[O-].[Na+].C1(CC1)NC1=C(C(=O)OCC)C=C(C(=N1)SC)F>>C1(CC1)N1C(NC(C2=C1N=C(C(=C2)F)SC)=O)=O
CCO[C:10]([c:6]1[c:5]([NH:15][CH:16]2[CH2:17][CH2:18]2)[n:4][c:3]([S:2][CH3:1])[c:8]([F:9])[cH:7]1)=[O:11].O=S(=O)(Cl)[N:12]=[C:13]=[O:14]>>[CH3:1][S:2][c:3]1[n:4][c:5]2[c:6]([cH:7][c:8]1[F:9])[c:10](=[O:11])[nH:12][c:13](=[O:14])[n:15]2[CH:16]1[CH2:17][CH2:18]1
CCOC(=O)c1cc(F)c(SC)nc1NC1CC1.O=C=NS(=O)(=O)Cl
CSc1nc2c(cc1F)c(=O)[nH]c(=O)n2C1CC1
null
null
ClCCl
Aromatic Heterocycle Formation
OtherReaction
5c0ad477af7d88500bf09ffb09fd74c76841c245ef9275b206c3966597586cbd
b2e640ad6adb277738cae8a944067d998d1107d1f884bf69b59d55eb50b99f16
O=c1[nH]c(=O)n(C2CC2)c2ncccc12
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[NH;D2;+0:6]-[C:7]1-[C:8]-[C:9]-1):[#7;a:10]:[c:11].Cl-S(=O)(=O)-[N;H0;D2;+0:12]=[C;H0;D2;+0:13]=[O;D1;H0:14]>>[O;D1;H0:2]=[c;H0;D3;+0:1]1:[nH;D2;+0:12]:[c;H0;D3;+0:13](=[O;D1;H0:14]):[n;H0;D3;+0:6](-[C:7]2-[C:8]-[C:9]-2):[c:5](:[#7;a:10]:[c:11]):[c:3]:1:[c:4]
18.5
[{"value": 18.5, "product": "C1(CC1)N1C(NC(C2=C1N=C(C(=C2)F)SC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-20
CELSIUS
3
HOUR
A solution of 4.1 g (15.2 mmol) of ethyl 2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinate (Example 34) in 125 mL of dichloromethane is cooled to −20° C. and treated dropwise with 5.24 g (37 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 3 hours and allowed to come to room temperature o...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
null
c1ccncc1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.C1CC1
HCl
ClCCl
-20
3
CCOC(=O)c1cc(F)c(SC)nc1NC1CC1.O=C=NS(=O)(=O)Cl>ClCCl>CSc1nc2c(cc1F)c(=O)[nH]c(=O)n2C1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-185d4e0e534448e7ba4c8a2b3a5896e9
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(Cl)c(F)cc12>>Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O
ClC=1C(=CC2=C(N(C(NC2=O)=O)C2CC2)N1)F.[H-].[Na+].[N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])NO>>NN1C(N(C2=C(C1=O)C=C(C(=N2)Cl)F)C2CC2)=O
O=[N+]([O-])c1ccc([NH:1]O)c([N+](=O)[O-])c1.[nH:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([Cl:10])[n:11][c:12]2[n:13]([CH:14]2[CH2:15][CH2:16]2)[c:17]1=[O:18]>>[NH2:1][n:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([Cl:10])[n:11][c:12]2[n:13]([CH:14]2[CH2:15][CH2:16]2)[c:17]1=[O:18]
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(Cl)c(F)cc12
Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O
null
null
CN(C=O)C.O1CCOCC1
Miscellaneous
OtherReaction
197fc1cd782bf0a9ab124bb6694fcd605cef406f0748e8fd9b8cb146776d967a
3bddf3a0255acf51e70359a0ac8208ce5eb2b81944f30a388fe53f3d9c8f01da
O=c1[nH]c(=O)n(C2CC2)c2ncccc12
O-[NH;D2;+0:1]-c1:c:c:c(-[N+](=O)-[O-]):c:c:1-[N+](=O)-[O-].[#7;a:2]:[c:3]1:[c:4]:[c:5](=[O;D1;H0:6]):[nH;D2;+0:7]:[c:8](=[O;D1;H0:9]):[#7;a:10]:1-[C:11]>>[#7;a:2]:[c:3]1:[c:4]:[c:5](=[O;D1;H0:6]):[n;H0;D3;+0:7](-[NH2;D1;+0:1]):[c:8](=[O;D1;H0:9]):[#7;a:10]:1-[C:11]
65.3
[{"value": 65.3, "product": "NN1C(N(C2=C(C1=O)C=C(C(=N2)Cl)F)C2CC2)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 3.83 g (15 mmol) of 7-chloro-1-cyclopropyl-6-fluoro-1H-pyrido[2,3-d]pyrimidine-2,4-dione (Example 23i) in 50 mL of dimethylformamide-dioxane (1:1) is cooled to 0° C. and treated portionwise with 0.8 g (20 mmol) of 60% sodium hydride/mineral oil. The reaction is stirred to room temperature for 30 minutes, ...
10.6084/m9.figshare.5104873.v1
null
Nitro group.Nitro group.Secondary amine
Primary amine
c1ccccc1.c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.C1CC1
HO-
CN(C=O)C.O1CCOCC1
null
0.5
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(Cl)c(F)cc12>CN(C=O)C.O1CCOCC1>Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4df6972c6e4c48278a3fccf487f8d5a4
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(S(=O)(O)=S)c(F)cc12>>Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O
[N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])NO.C1(CC1)N1C(NC(C2=C1N=C(C(=C2)F)S(=O)(O)=S)=O)=O.[H-].[Na+]>>NN1C(N(C2=C(C1=O)C=C(C(=N2)S(=O)(O)=S)F)C2CC2)=O
O=[N+]([O-])c1ccc([NH:1]O)c([N+](=O)[O-])c1.[nH:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([S:10](=[O:11])([OH:12])=[S:13])[n:14][c:15]2[n:16]([CH:17]2[CH2:18][CH2:19]2)[c:20]1=[O:21]>>[NH2:1][n:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([S:10](=[O:11])([OH:12])=[S:13])[n:14][c:15]2[n:16]([CH:17]2[CH2:18][CH2:19]...
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(S(=O)(O)=S)c(F)cc12
Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O
null
null
CN(C=O)C.O1CCOCC1
Miscellaneous
OtherReaction
197fc1cd782bf0a9ab124bb6694fcd605cef406f0748e8fd9b8cb146776d967a
3bddf3a0255acf51e70359a0ac8208ce5eb2b81944f30a388fe53f3d9c8f01da
O=c1[nH]c(=O)n(C2CC2)c2ncccc12
O-[NH;D2;+0:1]-c1:c:c:c(-[N+](=O)-[O-]):c:c:1-[N+](=O)-[O-].[#7;a:2]:[c:3]1:[c:4]:[c:5](=[O;D1;H0:6]):[nH;D2;+0:7]:[c:8](=[O;D1;H0:9]):[#7;a:10]:1-[C:11]>>[#7;a:2]:[c:3]1:[c:4]:[c:5](=[O;D1;H0:6]):[n;H0;D3;+0:7](-[NH2;D1;+0:1]):[c:8](=[O;D1;H0:9]):[#7;a:10]:1-[C:11]
76.7
[{"value": 76.7, "product": "NN1C(N(C2=C(C1=O)C=C(C(=N2)S(=O)(O)=S)F)C2CC2)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 0.47 g (1.57 mmol) of 1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid (Example 35) in 20 mL of dimethylformamide/dioxane (1:1) is treated portionwise with 0.08 g (2.0 mmol) of 60% sodium hydride/mineral oil. The reaction is stirred at room temperature for 1 ...
10.6084/m9.figshare.5104873.v1
null
Nitro group.Nitro group.Secondary amine
Primary amine
c1ccccc1.c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1cnc2ncncc2c1.C1CC1
HO-
CN(C=O)C.O1CCOCC1
null
1
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2nc(S(=O)(O)=S)c(F)cc12>CN(C=O)C.O1CCOCC1>Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9b30bb348856466e831c1ac5c92d19a5
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12>>Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O
[N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])NO.C1(CC1)N1C(NC(C2=CC(=C(C=C12)F)F)=O)=O.O1CCCC1.[H-].[Na+]>>NN1C(N(C2=CC(=C(C=C2C1=O)F)F)C1CC1)=O
O=[N+]([O-])c1ccc([NH:1]O)c([N+](=O)[O-])c1.[nH:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([F:10])[cH:11][c:12]2[n:13]([CH:14]2[CH2:15][CH2:16]2)[c:17]1=[O:18]>>[NH2:1][n:2]1[c:3](=[O:4])[c:5]2[cH:6][c:7]([F:8])[c:9]([F:10])[cH:11][c:12]2[n:13]([CH:14]2[CH2:15][CH2:16]2)[c:17]1=[O:18]
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12
Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O
null
null
CN(C=O)C.O1CCOCC1
Miscellaneous
OtherReaction
7d9afd8ce69d2cc21587dcf7a5296320785ec57dbd2625a7e8258b9a211370fb
3bddf3a0255acf51e70359a0ac8208ce5eb2b81944f30a388fe53f3d9c8f01da
O=c1[nH]c(=O)n(C2CC2)c2ccccc12
O-[NH;D2;+0:1]-c1:c:c:c(-[N+](=O)-[O-]):c:c:1-[N+](=O)-[O-].[C:2]-[#7;a:3]1:[c:4]:[c:5]:[c:6](=[O;D1;H0:7]):[nH;D2;+0:8]:[c:9]:1=[O;D1;H0:10]>>[C:2]-[#7;a:3]1:[c:4]:[c:5]:[c:6](=[O;D1;H0:7]):[n;H0;D3;+0:8](-[NH2;D1;+0:1]):[c:9]:1=[O;D1;H0:10]
null
[]
50
CELSIUS
25
MINUTE
To a solution of a 1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione (Example 23) in 1:1 dry tetrahydrofuran or dioxane and dry N,N-dimethylformamide is added portionwise sodium hydride (1.1 eq., 60% mineral oil dispersion) at room temperature. After stirring at 50° C. for 20 to 30 minutes, the resulting solution is ...
10.6084/m9.figshare.5104873.v1
null
Nitro group.Nitro group.Secondary amine
Primary amine
c1ccccc1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC1
HO-
CN(C=O)C.O1CCOCC1
50
0.416667
O=[N+]([O-])c1ccc(NO)c([N+](=O)[O-])c1.O=c1[nH]c(=O)n(C2CC2)c2cc(F)c(F)cc12>CN(C=O)C.O1CCOCC1>Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-73b7642ecef9423da7f5d61ee74ce612
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O>>CC(C)(C)OC(=O)N[C@H]1CCN(c2cc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
NN1C(N(C2=CC(=C(C=C2C1=O)F)F)C1CC1)=O.C(C)N(CC)CC.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O>>NN1C(N(C2=CC(=C(C=C2C1=O)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)C1CC1)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][NH:12][CH2:30]1.F[c:13]1[cH:14][c:15]2[c:16]([cH:17][c:18]1[F:19])[c:20](=[O:21])[n:22]([NH2:23])[c:24](=[O:25])[n:26]2[CH:27]1[CH2:28][CH2:29]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH...
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O
CC(C)(C)OC(=O)N[C@H]1CCN(c2cc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
7104773b13be215efb267302b4d954626cc11870e7067ef3d0293812a217ef67
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
F-[c;H0;D3;+0:1]1:[c:2]:[c:3]2:[#7;a:4](-[C:5]):[c:6]:[#7;a:7]:[c:8]:[c:9]:2:[c:10]:[c:11]:1-[F;D1;H0:12].[C:13]1-[C:14]-[NH;D2;+0:15]-[C:16]-[C:17]-1>>[C:5]-[#7;a:4]1:[c:6]:[#7;a:7]:[c:8]:[c:9]2:[c:10]:[c:11](-[F;D1;H0:12]):[c;H0;D3;+0:1](-[N;H0;D3;+0:15]3-[C:14]-[C:13]-[C:17]-[C:16]-3):[c:2]:[c:3]:1:2
88.2
[{"value": 88.2, "product": "NN1C(N(C2=CC(=C(C=C2C1=O)F)N1C[C@H](CC1)NC(=O)OC(C)(C)C)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 3-amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione (Example 24a) (50.0 mg, 0.20 mmol) and triethylamine (74 mg, 0.74 mmol) in acetonitrile (3 mL) is added (S)-pyrrolidin-3-yl carbamic acid tert-butyl ester (74 mg, 0.40 mmol). The solution is refluxed for 18 hours, the solvent is removed under ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(F)cc2n(C2CC2)c1=O>C(C)#N>CC(C)(C)OC(=O)N[C@H]1CCN(c2cc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-950eac8099204e9080cda488ff8ca284
NC(=O)c1cc(F)c(Cl)nc1Cl.NC1CC1.O=C(Cl)C(=O)Cl>>O=C(NC(=O)c1cc(F)c(Cl)nc1Cl)NC1CC1
C1(CC1)N.ClC1=C(C(=O)N)C=C(C(=N1)Cl)F.C(C(=O)Cl)(=O)Cl>>C1(CC1)NC(=O)NC(=O)C=1C(=NC(=C(C1)F)Cl)Cl
[NH2:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([Cl:11])[n:12][c:13]1[Cl:14].[NH2:15][CH:16]1[CH2:17][CH2:18]1.O=C(Cl)[C:2](Cl)=[O:1]>>[O:1]=[C:2]([NH:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([Cl:11])[n:12][c:13]1[Cl:14])[NH:15][CH:16]1[CH2:17][CH2:18]1
NC(=O)c1cc(F)c(Cl)nc1Cl.NC1CC1.O=C(Cl)C(=O)Cl
O=C(NC(=O)c1cc(F)c(Cl)nc1Cl)NC1CC1
null
null
ClCCl
Acylation
OtherReaction
e577f99702a17443c4b63368819f851a2e250f46104b0e197927714259e13f75
9d850324b70133759eb17211f422ea0eaaa4ed393624ec3b50fcd43d8091d8bd
O=C(NC(=O)c1cccnc1)NC1CC1
Cl-C(=O)-[C;H0;D3;+0:1](-Cl)=[O;D1;H0:2].[#7;a:3]:[c:4]:[c:5]-[C:6](-[NH2;D1;+0:7])=[O;D1;H0:8].[NH2;D1;+0:9]-[C:10]1-[C:11]-[C:12]-1>>[#7;a:3]:[c:4]:[c:5]-[C:6](=[O;D1;H0:8])-[NH;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[C:10]1-[C:11]-[C:12]-1
98.5
[{"value": 98.5, "product": "C1(CC1)NC(=O)NC(=O)C=1C(=NC(=C(C1)F)Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-20
CELSIUS
0.5
HOUR
A solution of 5.8 g (27.8 mmol) of 2,6-dichloro-5-fluoronicotinamide (Chem. Pharm. Bull., 1987; 35:2280) in 60 mL of dichloromethane is treated dropwise with 5.1 g (40 mmol) of oxalyl chloride, and the reaction mixture is heated at reflux for 18 hours. The solvent is removed in vacuo, and the residue is dissolved in 50...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Primary amide.Primary amine
Urea
null
null
c1ccncc1.C1CC1
HCl
ClCCl
-20
0.5
NC(=O)c1cc(F)c(Cl)nc1Cl.NC1CC1.O=C(Cl)C(=O)Cl>ClCCl>O=C(NC(=O)c1cc(F)c(Cl)nc1Cl)NC1CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d0534481b2c24568a736f1aa50104b5f
COc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>>COc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
NN1C(N(C2=C(C(=C(C=C2C1=O)F)F)OC)C1CC1)=O.C(C)(C)(C)OC(N[C@@H](C)[C@H]1CNCC1)=O.C(C)N(CC)CC.CS(=O)C>>C(C)(C)(C)OC(N[C@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1OC)C1CC1)=O)N)=O)F)=O
F[c:4]1[c:3]([O:2][CH3:1])[c:34]2[c:23]([cH:22][c:20]1[F:21])[c:24](=[O:25])[n:26]([NH2:27])[c:28](=[O:29])[n:30]2[CH:31]1[CH2:32][CH2:33]1.[NH:5]1[CH2:6][CH2:7][C@@H:8]([C@H:9]([CH3:10])[NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[CH2:19]1>>[CH3:1][O:2][c:3]1[c:4]([N:5]2[CH2:6][CH2:7][C@H:8]([C@@H:9...
COc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1
COc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
null
null
O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
7104773b13be215efb267302b4d954626cc11870e7067ef3d0293812a217ef67
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9](-[C:10]):[c:11]:2:[c:12]:1-[#8:13].[C:14]1-[C:15]-[C:16]-[C:17]-[NH;D2;+0:18]-1>>[#8:13]-[c:12]1:[c:11]2:[#7;a:9](-[C:10]):[c:8]:[#7;a:7]:[c:6]:[c:5]:2:[c:4]:[c:2](-[F;D1;H0:3]):[c;H0;D3;+0:1]:1-[N;H0;D3;+0:18]1-[C:14]-[C:15]-[C:16]-[C:17]...
96.3
[{"value": 96.3, "product": "C(C)(C)(C)OC(N[C@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1OC)C1CC1)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 0.57 g (2.0 mmol) of 3-amino-1-cyclopropyl-6,7-difluoro-8-methoxy-1H-quinazoline-2,4-dione (Example 24d), 0.64 g (3.0 mmol) of ((S)-(R)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.81 g (8.0 mmol) of triethylamine and 10 mL of dimethyl sulfoxide is heated at 110°...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1ccc2ncncc2c1.C1CCNC1
C1CC[NH]C1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HF
O
null
null
COc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>O>COc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a0bbca28098c41ebaaa22e11a823a20d
C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>>Cc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
N1CCCC1.C(C)N(CC)CC.NN1C(N(C2=C(C(=C(C=C2C1=O)F)F)C)C1CC1)=O.C(C)(C)(C)OC(N[C@@H](C)[C@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)(C)(C)OC(N[C@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1C)C1CC1)=O)N)=O)F)=O
[NH:4]1[CH2:5][CH2:6][C@@H:7]([C@H:8]([CH3:9])[NH:10][C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18]1.F[c:3]1[c:2]([CH3:1])[c:33]2[c:22]([cH:21][c:19]1[F:20])[c:23](=[O:24])[n:25]([NH2:26])[c:27](=[O:28])[n:29]2[CH:30]1[CH2:31][CH2:32]1>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][C@H:7]([C@@H:8]([CH3:9])[...
C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
Cc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
null
null
CS(=O)C.O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
7104773b13be215efb267302b4d954626cc11870e7067ef3d0293812a217ef67
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9](-[C:10]):[c:11]:2:[c:12]:1-[C;D1;H3:13].[C:14]1-[C:15]-[C:16]-[C:17]-[NH;D2;+0:18]-1>>[C:10]-[#7;a:9]1:[c:8]:[#7;a:7]:[c:6]:[c:5]2:[c:4]:[c:2](-[F;D1;H0:3]):[c;H0;D3;+0:1](-[N;H0;D3;+0:18]3-[C:14]-[C:15]-[C:16]-[C:17]-3):[c:12](-[C;D1;H3:1...
45.6
[{"value": 45.6, "product": "C(C)(C)(C)OC(N[C@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1C)C1CC1)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
120
CELSIUS
null
null
A solution of 0.5 g (1.9 mmol) of 3-amino-1-cyclopropyl-6,7-difluoro-8-methyl-1H-quinazoline-2,4-dione (Example 24e), 0.64 g (3.0 mmol) of ((S)-(R)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester, 0.81 g (8.0 mmol) of triethylamine and 10 mL of dimethyl sulfoxide is heated at 110° C. for 24 hours. After thin laye...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HF
CS(=O)C.O
120
null
C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>CS(=O)C.O>Cc1c(N2CC[C@H]([C@@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4b89529cfade46778b1112e883018c13
C[C@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>>Cc1c(N2CC[C@H]([C@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
N1CCCC1.C(C)N(CC)CC.NN1C(N(C2=C(C(=C(C=C2C1=O)F)F)C)C1CC1)=O.C(C)(C)(C)OC(N[C@@H](C)[C@@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)(C)(C)OC(N[C@@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1C)C1CC1)=O)N)=O)F)=O
[NH:4]1[CH2:5][CH2:6][C@H:7]([C@H:8]([CH3:9])[NH:10][C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18]1.F[c:3]1[c:2]([CH3:1])[c:33]2[c:22]([cH:21][c:19]1[F:20])[c:23](=[O:24])[n:25]([NH2:26])[c:27](=[O:28])[n:29]2[CH:30]1[CH2:31][CH2:32]1>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][C@H:7]([C@H:8]([CH3:9])[NH...
C[C@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
Cc1c(N2CC[C@H]([C@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
null
null
CS(=O)C.O
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
7104773b13be215efb267302b4d954626cc11870e7067ef3d0293812a217ef67
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n(C2CC2)c2cc(N3CCCC3)ccc12
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9](-[C:10]):[c:11]:2:[c:12]:1-[C;D1;H3:13].[C:14]1-[C:15]-[C:16]-[C:17]-[NH;D2;+0:18]-1>>[C:10]-[#7;a:9]1:[c:8]:[#7;a:7]:[c:6]:[c:5]2:[c:4]:[c:2](-[F;D1;H0:3]):[c;H0;D3;+0:1](-[N;H0;D3;+0:18]3-[C:14]-[C:15]-[C:16]-[C:17]-3):[c:12](-[C;D1;H3:1...
52.5
[{"value": 52.5, "product": "C(C)(C)(C)OC(N[C@@H](C)[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N(C2=C1C)C1CC1)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
120
CELSIUS
null
null
A solution of 0.5 g (1.9 mmol) of 3-amino-1-cyclopropyl-6,7-difluoro-8-methyl-1H-quinazoline-2,4-dione (Example 24e), 0.64 g (3.0 mmol) of ((S)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester, 0.81 g (8.0 mmol) of triethylamine and 10 mL of dimethyl sulfoxide is heated at 110° C. for 24 hours. After thin laye...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1
C1CC[NH]C1.c1ccc2ncncc2c1.C1CC1
HF
CS(=O)C.O
120
null
C[C@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Cc1c(F)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12>CS(=O)C.O>Cc1c(N2CC[C@H]([C@H](C)NC(=O)OC(C)(C)C)C2)c(F)cc2c(=O)n(N)c(=O)n(C3CC3)c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e85e2ebb798446ffac97f400cdc25983
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23>>CC1COc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
NN1C(N2C(COC=3C(=C(C=C(C1=O)C32)F)F)C)=O.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)(C)(C)OC(N[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N3C(COC1=C32)C)=O)N)=O)F)=O
[NH:7]1[CH2:8][CH2:9][C@H:10]([NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[CH2:19]1.F[c:6]1[c:5]2[c:31]3[c:23]([cH:22][c:20]1[F:21])[c:24](=[O:25])[n:26]([NH2:27])[c:28](=[O:29])[n:30]3[CH:2]([CH3:1])[CH2:3][O:4]2>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([N:7]3[CH2:8][CH2:9][C@H:10]([NH:11][C:12](=[O:1...
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23
CC1COc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
da3d3dafeb9a0bcdf43850d6bbb3b56cb42f37c79a7b655b09d7a5a6d1690337
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n2c3c(c(N4CCCC4)ccc13)OCC2
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]3:[c:10]:2:[c:11]:1-[#8:12]-[C:13]-[C:14]-3.[C:15]1-[C:16]-[NH;D2;+0:17]-[C:18]-[C:19]-1>>[F;D1;H0:3]-[c:2]1:[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]3:[c:10]:2:[c:11](:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:17]1-[C:16]-[C:15]-[C:19]-[C:18]-1)-[#8:1...
104.1
[{"value": 104.1, "product": "C(C)(C)(C)OC(N[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N3C(COC1=C32)C)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 0.2 g (0.75 mmol) of 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione (Example 24h), 0.58 g (2.0 mmol) of (S)-3-pyrrolidinylcarbamic acid tert-butyl ester (J. Med. Chem., 1992; 35:1764), 0.5 g (0.5 mmol) of triethylamine and 20 mL of acetonitrile is heated at reflux for 18 hou...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1cc2c3c(cncn3[CH]CO2)c1
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CO2)c1
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CO2)c1
HF
C(C)#N
null
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23>C(C)#N>CC1COc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b8b2453d6ea8466d8369d3d209d68ab2
CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1>>CC1COc2c(N3CC[C@@H]([C@H](C)NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
NN1C(N2C(COC=3C(=C(C=C(C1=O)C32)F)F)C)=O.C(C)(C)(C)OC(N[C@H](C)[C@@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)(C)(C)OC(N[C@@H](C)[C@H]1CN(CC1)C1=C(C=C2C(N(C(N3C(COC1=C32)C)=O)N)=O)F)=O
F[c:6]1[c:5]2[c:33]3[c:25]([cH:24][c:22]1[F:23])[c:26](=[O:27])[n:28]([NH2:29])[c:30](=[O:31])[n:32]3[CH:2]([CH3:1])[CH2:3][O:4]2.[NH:7]1[CH2:8][CH2:9][C@H:10]([C@@H:11]([CH3:12])[NH:13][C:14](=[O:15])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:21]1>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([N:7]3[CH2:8][CH2:9][C@@H:10]...
CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1
CC1COc2c(N3CC[C@@H]([C@H](C)NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
da3d3dafeb9a0bcdf43850d6bbb3b56cb42f37c79a7b655b09d7a5a6d1690337
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n2c3c(c(N4CCCC4)ccc13)OCC2
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]3:[c:10]:2:[c:11]:1-[#8:12]-[C:13]-[C:14]-3.[C:15]1-[C:16]-[NH;D2;+0:17]-[C:18]-[C:19]-1>>[F;D1;H0:3]-[c:2]1:[c:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]3:[c:10]:2:[c:11](:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:17]1-[C:16]-[C:15]-[C:19]-[C:18]-1)-[#8:1...
73.7
[{"value": 73.7, "product": "C(C)(C)(C)OC(N[C@@H](C)[C@H]1CN(CC1)C1=C(C=C2C(N(C(N3C(COC1=C32)C)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 0.11 g (0.41 mmol) of 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione (Example 24h), 0.26 g (1.3 mmol) of ((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.25 g (2.5 mmol) of triethylamine and 10 mL of acetonitrile is heated at r...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1cc2c3c(cncn3[CH]CO2)c1.C1CCNC1
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CO2)c1
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CO2)c1
HF
C(C)#N
null
null
CC1COc2c(F)c(F)cc3c(=O)n(N)c(=O)n1c23.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1>C(C)#N>CC1COc2c(N3CC[C@@H]([C@H](C)NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7529c8caf4b748479316487eac532aa3
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1(N)CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23>>CC1CCc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
NC1(CCC=2C(=C(C=C3C(NC(N1C23)=O)=O)F)F)C.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O.C(C)N(CC)CC.CS(=O)C>>C(C)(C)(C)OC(N[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N3C2=C1CCC3C)=O)N)=O)F)=O
[NH:7]1[CH2:8][CH2:9][C@H:10]([NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[CH2:19]1.F[c:6]1[c:5]2[c:31]3[c:23]([cH:22][c:20]1[F:21])[c:24](=[O:25])[nH:26][c:28](=[O:29])[n:30]3[C:2]([CH3:1])([NH2:27])[CH2:3][CH2:4]2>>[CH3:1][CH:2]1[CH2:3][CH2:4][c:5]2[c:6]([N:7]3[CH2:8][CH2:9][C@H:10]([NH:11][C:12](=...
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1(N)CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23
CC1CCc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
8b927508496a2bc8ede2a5265948ea4c2027370901c2ab699177b34dfe97a5fa
3e73feb1dca6e66ea9b3917426713f608e758767b2fa3bbf3ea155f54ecc0d2a
O=c1[nH]c(=O)n2c3c(c(N4CCCC4)ccc13)CCC2
F-[c;H0;D3;+0:1]1:[c:2](-[F;D1;H0:3]):[c:4]:[c:5]2:[c:6](=[O;D1;H0:7]):[nH;D2;+0:8]:[c:9](=[O;D1;H0:10]):[#7;a:11]3:[c:12]:2:[c:13]:1-[C:14]-[C:15]-[C;H0;D4;+0:16]-3(-[C;D1;H3:17])-[NH2;D1;+0:18].[C:19]1-[C:20]-[NH;D2;+0:21]-[C:22]-[C:23]-1>>[C;D1;H3:17]-[CH;D3;+0:16]1-[C:15]-[C:14]-[c:13]2:[c:12]3:[#7;a:11]-1:[c:9](=[...
71.8
[{"value": 71.8, "product": "C(C)(C)(C)OC(N[C@@H]1CN(CC1)C1=C(C=C2C(N(C(N3C2=C1CCC3C)=O)N)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 0.12 g (0.45 mmol) of 5-amino-8,9-difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dione (Example 24i), 0.34 g (1.8 mmol) of (S)-3-pyrrolidinylcarbamic acid tert-butyl ester (J. Med. Chem., 1992; 35:1764), 0.2 g (2.0 mmol) of triethylamine and 7 mL of dimethyl sulfoxide is heated at 110° C...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine.Secondary amine
Primary amine.Tertiary amine
C1CCNC1.C1CCc2cccc3cncn1c23
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CC2)c1
C1CC[NH]C1.c1cc2c3c(cncn3[CH]CC2)c1
HF
O
null
1
CC(C)(C)OC(=O)N[C@H]1CCNC1.CC1(N)CCc2c(F)c(F)cc3c(=O)[nH]c(=O)n1c23>O>CC1CCc2c(N3CC[C@H](NC(=O)OC(C)(C)C)C3)c(F)cc3c(=O)n(N)c(=O)n1c23
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2ab82c696e84490ebe8f5ae057f63112
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O>>CC(C)(C)OC(=O)NC1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
NN1C(N(C2=C(C1=O)C=C(C(=N2)Cl)F)C2CC2)=O.C(C)(C)(C)OC(N[C@@H]1CNCC1)=O.C(C)(C)N(C(C)C)CC.C(C)#N>>C(C)(C)(C)OC(NC1CN(CC1)C=1C(=CC2=C(N(C(N(C2=O)N)=O)C2CC2)N1)F)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][CH2:11][NH:12][CH2:30]1.Cl[c:13]1[n:14][c:15]2[c:16]([cH:17][c:18]1[F:19])[c:20](=[O:21])[n:22]([NH2:23])[c:24](=[O:25])[n:26]2[CH:27]1[CH2:28][CH2:29]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][N:12]([c:13]2[n:1...
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O
CC(C)(C)OC(=O)NC1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
null
null
O
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
8d4ca8461a6b23e91ba625c70adedcf11c9bf5e1ce707c6f73890ac66ced0170
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1[nH]c(=O)n(C2CC2)c2nc(N3CCCC3)ccc12
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]:[#7;a:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[C:12]-[C:11]-1):[c:5](-[F;D1;H0:6]):[c:7]
83.2
[{"value": 83.2, "product": "C(C)(C)(C)OC(NC1CN(CC1)C=1C(=CC2=C(N(C(N(C2=O)N)=O)C2CC2)N1)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
A solution of 0.11 g (0.4 mmol) of 3-amino-7-chloro-1-cyclopropyl-6-fluoro-1H-pyrido[2,3-d]pyrimidine-2,4-dione (Example 24b), 0.105 g (0.56 mmol) of (S)-3-pyrrolidinylcarbamic acid tert-butyl ester (J. Med. Chem., 1992; 35:1764), 1.2 mL of N,N-diisopropylethylamine and 3 mL of acetonitrile is heated at 50° C. for 18 h...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1cnc2ncncc2c1
C1CC[NH]C1.c1cnc2ncncc2c1
C1CC[NH]C1.c1cnc2ncncc2c1.C1CC1
HCl
O
0
null
CC(C)(C)OC(=O)N[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(Cl)nc2n(C2CC2)c1=O>O>CC(C)(C)OC(=O)NC1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7617c6a9714f4fc1badb4dccedb07ffc
C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O>>C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
NN1C(N(C2=C(C1=O)C=C(C(=N2)S(=O)(O)=S)F)C2CC2)=O.NN1C(N(C2=C(C1=O)C=C(C(=N2)S(=O)(O)=S)F)C2CC2)=O.C(C)(C)(C)OC(N[C@H](C)[C@@H]1CNCC1)=O.C(C)N(CC)CC>>C(C)(C)(C)OC(N[C@@H](C)[C@H]1CN(CC1)C=1C(=CC2=C(N(C(N(C2=O)N)=O)C2CC2)N1)F)=O
[CH3:1][C@@H:2]([NH:3][C:4](=[O:5])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10])[C@H:11]1[CH2:12][CH2:13][NH:14][CH2:32]1.O=S(O)(=S)[c:15]1[n:16][c:17]2[c:18]([cH:19][c:20]1[F:21])[c:22](=[O:23])[n:24]([NH2:25])[c:26](=[O:27])[n:28]2[CH:29]1[CH2:30][CH2:31]1>>[CH3:1][C@H:2]([NH:3][C:4](=[O:5])[O:6][C:7]([CH3:8])([CH3:9])[CH3:1...
C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O
C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
9048cbc1d11fe70a6a6f1ef740f2b1a546c5fb7a8d7b85bfb8434536f406efb7
7cc25fba33369069673bac5bd8fc404dc064da8d6c8cf4a77f21f4df0a617fe3
O=c1[nH]c(=O)n(C2CC2)c2nc(N3CCCC3)ccc12
O-S(=O)(=S)-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]:[#7;a:4]):[c:5](-[F;D1;H0:6]):[c:7].[C:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-1>>[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[C:8]-[C:12]-1):[c:5](-[F;D1;H0:6]):[c:7]
58.7
[{"value": 58.7, "product": "C(C)(C)(C)OC(N[C@@H](C)[C@H]1CN(CC1)C=1C(=CC2=C(N(C(N(C2=O)N)=O)C2CC2)N1)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A solution of 0.12 g (0.38 mmol) of 3-amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid (Compound 24c) in 10 mL of acetonitrile is treated with 0.24 g (1.14 mmol) of ((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.25 g ...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Tertiary amine
C1CCNC1.c1cnc2ncncc2c1
C1CC[NH]C1.c1cnc2ncncc2c1
C1CC[NH]C1.c1cnc2ncncc2c1.C1CC1
Other
C(C)#N
null
18
C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1.Nn1c(=O)c2cc(F)c(S(=O)(O)=S)nc2n(C2CC2)c1=O>C(C)#N>C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCN(c2nc3c(cc2F)c(=O)n(N)c(=O)n3C2CC2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b845dd2edd604c6ea501e182a83263a2
CC1COc2c(ccc(F)c2F)N1.NO.OC(O)C(Cl)(Cl)Cl>>CC1COc2c(ccc(F)c2F)N1C(=O)C=NO
FC1=C(C2=C(NC(CO2)C)C=C1)F.Cl.Cl.NO.ClC(C(O)O)(Cl)Cl.O.O.O.O.O.O.O.O.O.O.S(=O)(=O)([O-])[O-].[Na+].[Na+]>>FC1=C(C2=C(N(C(CO2)C)C(C=NO)=O)C=C1)F
[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([cH:7][cH:8][c:9]([F:10])[c:11]2[F:12])[NH:13]1.[NH2:17][OH:18].O[CH:16]([C:14](Cl)(Cl)Cl)[OH:15]>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([cH:7][cH:8][c:9]([F:10])[c:11]2[F:12])[N:13]1[C:14](=[O:15])[CH:16]=[N:17][OH:18]
CC1COc2c(ccc(F)c2F)N1.NO.OC(O)C(Cl)(Cl)Cl
CC1COc2c(ccc(F)c2F)N1C(=O)C=NO
null
null
O
Acylation
OtherReaction
dfadd1c6df8f6d5a29d1115292936c8f1451835bff21769cf44d26ae746a2c72
52aca9b4c7d973694a75a6b6433690467b1da39a97cb47a62061db06e1a5716b
c1ccc2c(c1)NCCO2
Cl-[C;H0;D4;+0:1](-Cl)(-Cl)-[CH;D3;+0:2](-O)-[OH;D1;+0:3].[C;D1;H3:4]-[C:5]1-[C:6]-[#8:7]-[c:8]:[c:9](:[c:10])-[NH;D2;+0:11]-1.[NH2;D1;+0:12]-[O;D1;H1:13]>>[C;D1;H3:4]-[C:5]1-[C:6]-[#8:7]-[c:8]:[c:9](:[c:10])-[N;H0;D3;+0:11]-1-[C;H0;D3;+0:1](=[O;H0;D1;+0:3])-[CH;D2;+0:2]=[N;H0;D2;+0:12]-[O;D1;H1:13]
null
[]
77.5
CELSIUS
null
null
A solution of 8.27 g (50 mmol) of chloral hydrate in 125 mL of water is treated with 112.8 g (0.35 mmol) of sodium sulfate decahydrate. The mixture is stirred and treated with a solution of 7,8-difluoro-3-methyl-3,4-dihydro-2H-benz[1,4]oxazine (Chem. Pharm. Bull., 1984; 32:4907) hydrochloride (prepared by dissolving 8....
10.6084/m9.figshare.5104873.v1
null
Trichloro group.Secondary alcohol.Secondary alcohol.Primary amine.Secondary amine
Tertiary amide.Oxime
c1ccc2c(c1)NCCO2
c1ccc2c(c1)[NH]CCO2
c1ccc2c(c1)[NH]CCO2
HCl
O
77.5
null
CC1COc2c(ccc(F)c2F)N1.NO.OC(O)C(Cl)(Cl)Cl>O>CC1COc2c(ccc(F)c2F)N1C(=O)C=NO
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-053cc80fe9db4fb8b511eee6cdeb80be
CC1COc2c(ccc(F)c2F)N1C(=O)C=NO>>CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O
FC1=C(C2=C(N(C(CO2)C)C(C=NO)=O)C=C1)F.S(O)(O)(=O)=O>>FC1=C2OCC(N3C(C(C(C=C1F)=C32)=O)=O)C
N(=[CH:16][C:14]([N:13]1[CH:2]([CH3:1])[CH2:3][O:4][c:5]2[c:6]([F:7])[c:8]([F:9])[cH:10][cH:11][c:12]21)=[O:15])[OH:17]>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([F:7])[c:8]([F:9])[cH:10][c:11]3[c:12]2[N:13]1[C:14](=[O:15])[C:16]3=[O:17]
CC1COc2c(ccc(F)c2F)N1C(=O)C=NO
CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
33b99c785a6c3c3568e3962623beb70c587545568ab3138e400dfd91fdc147c6
ab4bf08516e66cf6fd8670ac9e8d4ecd074b35f40b66b51c2d0c9c0d98ab1c51
O=C1C(=O)N2CCOc3cccc1c32
[#8:1]-[c:2]:[c:3](:[cH;D2;+0:4]:[c:5]:[c:6])-[#7:7](-[C:8](=[O;D1;H0:9])-[CH;D2;+0:10]=N-[OH;D1;+0:11])-[C:12]>>[#8:1]-[c:2]:[c:3]1:[c;H0;D3;+0:4](:[c:5]:[c:6])-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-[C:8](=[O;D1;H0:9])-[#7:7]-1-[C:12]
null
[]
80
CELSIUS
null
null
A solution of 45 mL of 98% sulfuric acid in 18 mL of water is heated to 50° C. to 60° C. and treated portionwise over 30 minutes with 10.5 g (41 mmol) of (7,8-difluoro-3-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)oxoacetaldehyde oxime (Example 29). After the addition is complete, the reaction is heated to 80° C. for 15 min...
10.6084/m9.figshare.5104873.v1
null
Oxime
Ketone
c1ccc2c(c1)[NH]CCO2
c1cc2c3c(c1)OCCN3CC2
c1cc2c3c(c1)OCCN3CC2
Other
O
80
null
CC1COc2c(ccc(F)c2F)N1C(=O)C=NO>O>CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4fd926229a494c629b68840a11ffe7c1
CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O.OO>>CC1COc2c(F)c(F)cc(C(=O)O)c2N1
FC1=C2OCC(N3C(C(C(C=C1F)=C32)=O)=O)C.OO>>FC=1C(=C2C(NC(CO2)C)=C(C1)C(=O)O)F
O=C1[C:12](=[O:13])[c:11]2[cH:10][c:8]([F:9])[c:6]([F:7])[c:5]3[c:15]2[N:16]1[CH:2]([CH3:1])[CH2:3][O:4]3.O[OH:14]>>[CH3:1][CH:2]1[CH2:3][O:4][c:5]2[c:6]([F:7])[c:8]([F:9])[cH:10][c:11]([C:12](=[O:13])[OH:14])[c:15]2[NH:16]1
CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O.OO
CC1COc2c(F)c(F)cc(C(=O)O)c2N1
null
null
[OH-].[Na+]
Acylation
OtherReaction
331c26160f350780d6eb268d594f92792ab2a64f9a9c14591cbe111e0c7b4f03
74f47597d04f1974e1889dc872a1ecf734a11acc7611e0fce2bef841101f8996
c1ccc2c(c1)NCCO2
O-[OH;D1;+0:1].O=C1-[C;H0;D3;+0:2](=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]2:[c:7]-[#8:8]-[C:9]-[C:10](-[C;D1;H3:11])-[N;H0;D3;+0:12]-1-2>>[C;D1;H3:11]-[C:10]1-[C:9]-[#8:8]-[c:7]:[c:6](:[c:4](-[C;H0;D3;+0:2](=[O;D1;H0:3])-[OH;D1;+0:1]):[c:5])-[NH;D2;+0:12]-1
null
[]
5
CELSIUS
null
null
A suspension of 6.9 g (28.8 mmol) of 6,7-difluoro-3-methyl-3,4-dihydro-5-oxa-2a-aza-acenaphthylene-1,2-dione (Example 30) in 250 mL of 4.5% aqueous sodium hydroxide is treated dropwise with 16.4 mL of 30% hydrogen peroxide over 1 hour. The reaction is filtered to remove a trace of insoluble material and the filtrate is...
10.6084/m9.figshare.5104873.v1
null
Ketone.Tertiary amide.Peroxide
Carboxylic acid.Secondary amine
c1cc2c3c(c1)OCCN3CC2
c1ccc2c(c1)NCCO2
c1ccc2c(c1)NCCO2
Other
[OH-].[Na+]
5
null
CC1COc2c(F)c(F)cc3c2N1C(=O)C3=O.OO>[OH-].[Na+]>CC1COc2c(F)c(F)cc(C(=O)O)c2N1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cf7993e3573e421a894de7cb83cffe3e
COC(=O)c1cc(F)c(F)c2ccc(C)nc12>>COC(=O)c1cc(F)c(F)c2c1NC(C)CC2
COC(=O)C=1C=C(C(=C2C=CC(=NC12)C)F)F.O.[H][H]>>COC(=O)C=1C=C(C(=C2CCC(NC12)C)F)F
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([F:8])[c:9]([F:10])[c:11]2[c:12]1[n:13][c:14]([CH3:15])[cH:16][cH:17]2>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([F:8])[c:9]([F:10])[c:11]2[c:12]1[NH:13][CH:14]([CH3:15])[CH2:16][CH2:17]2
COC(=O)c1cc(F)c(F)c2ccc(C)nc12
COC(=O)c1cc(F)c(F)c2c1NC(C)CC2
null
[Pt]
C(C)(=O)O
Reduction
OtherReaction
0f501d7f6563b973124f46b9ac99227bf4e9d23710ef3fe61283d96ce59150d0
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc2c(c1)CCCN2
[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]1:[n;H0;D2;+0:6]:[c;H0;D3;+0:7](-[C;D1;H3:8]):[cH;D2;+0:9]:[cH;D2;+0:10]:[c:11]:1:[c:12]>>[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]1:[c:11](:[c:12])-[CH2;D2;+0:10]-[CH2;D2;+0:9]-[CH;D3;+0:7](-[C;D1;H3:8])-[NH;D2;+0:6]-1
68.9
[{"value": 68.9, "product": "COC(=O)C=1C=C(C(=C2CCC(NC12)C)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 8.0 g (33.7 mmol) of 5,6-difluoro-2-methylquinoline-8-carboxylic acid methyl ester (Example 33) in 100 mL of glacial acetic acid is treated with 2.15 g of platinum on carbon (0.8 g of active catalyst+62.8% water) and then shaken in a hydrogen atmosphere at temperatures of 24° C. to 29° C. and pressures of...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2ncccc2c1
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCCN2
null
[Pt].C(C)(=O)O
null
null
COC(=O)c1cc(F)c(F)c2ccc(C)nc12>[Pt].C(C)(=O)O>COC(=O)c1cc(F)c(F)c2c1NC(C)CC2
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2f6822f4b3d84e5c8faab5b8723b6257
CCOC(=O)c1cc(F)c(SC)nc1Cl.NC1CC1>>CCOC(=O)c1cc(F)c(SC)nc1NC1CC1
C(C)OC(C1=C(N=C(C(=C1)F)SC)Cl)=O.C1(CC1)N.C1(CC1)N>>C(C)OC(C1=C(N=C(C(=C1)F)SC)NC1CC1)=O
Cl[c:14]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][c:8]([F:9])[c:10]([S:11][CH3:12])[n:13]1.[NH2:15][CH:16]1[CH2:17][CH2:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([F:9])[c:10]([S:11][CH3:12])[n:13][c:14]1[NH:15][CH:16]1[CH2:17][CH2:18]1
CCOC(=O)c1cc(F)c(SC)nc1Cl.NC1CC1
CCOC(=O)c1cc(F)c(SC)nc1NC1CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c026a7bf7aba66b20cf21a13c528689aaaa1c05901524d62b36ca0c3b0572cef
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NC2CC2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8]):[c:9].[NH2;D1;+0:10]-[C:11]1-[C:12]-[C:13]-1>>[C:8]-[#8:7]-[C:5](=[O;D1;H0:6])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C:11]1-[C:12]-[C:13]-1):[#7;a:2]:[c:3]
69.1
[{"value": 69.1, "product": "C(C)OC(C1=C(N=C(C(=C1)F)SC)NC1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
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A solution of 8.7 g (34.8 mmol) of 2-chloro-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester (J. Med. Chem., 1993; 36:2676) and 5.7 g (100 mmol) of cyclopropylamine in 100 mL of acetonitrile is heated at reflux for 18 hours. After TLC showed the presence of unreacted starting material, 4.12 g (72 mmol) of cyclopropy...
10.6084/m9.figshare.5104873.v1
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Aromatic halide.Primary amine
Secondary amine
c1ccncc1
c1ccncc1
c1ccncc1.C1CC1
HCl
C(C)#N
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CCOC(=O)c1cc(F)c(SC)nc1Cl.NC1CC1>C(C)#N>CCOC(=O)c1cc(F)c(SC)nc1NC1CC1