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
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14
3.37k
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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-5f42e2530e154a3096b9b9ddf20e8732
BrP(Br)Br.CC(C)(C)OC(=O)n1ccc2c(CO)cccc21>>CC(C)(C)OC(=O)n1ccc2c(CBr)cccc21
P(Br)(Br)Br.C(=O)(OC(C)(C)C)N1C=CC2=C(C=CC=C12)CO.C(=O)(O)[O-].[Na+]>>BrCC1=C2C=CN(C2=CC=C1)C(=O)OC(C)(C)C
BrP(Br)[Br:14].O[CH2:13][c:12]1[c:11]2[cH:10][cH:9][n:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[c:18]2[cH:17][cH:16][cH:15]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[n:8]1[cH:9][cH:10][c:11]2[c:12]([CH2:13][Br:14])[cH:15][cH:16][cH:17][c:18]12
BrP(Br)Br.CC(C)(C)OC(=O)n1ccc2c(CO)cccc21
CC(C)(C)OC(=O)n1ccc2c(CBr)cccc21
null
null
C(Cl)Cl.CCOCC
Functional Group Interconversion
PBr3 and alcohol to alkyl bromide
bb752b9027dc4488ba075e5955118a819f80cabd751a7497b67c2eeb1db6b071
cbf41c7cf9fe6b47a243b1674d74ed5bf46a151f7f3a71d206e23176e158facf
c1ccc2[nH]ccc2c1
Br-P(-Br)-[Br;H0;D1;+0:1].O-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]:[c:6]:[#7;a:7]>>[#7;a:7]:[c:6]:[c:5]:[c:3](-[CH2;D2;+0:2]-[Br;H0;D1;+0:1]):[c:4]
84
[{"value": 84.0, "product": "BrCC1=C2C=CN(C2=CC=C1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.6, "product": "BrCC1=C2C=CN(C2=CC=C1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
PBr3 (2.4 mL. 25.8 mmol) was added dropwise at 0° C. under nitrogen to a stirred solution of tert-butyl 4-(hydroxymethyl) 1H-1-indolecarboxylate 6 (6.0 g, 24.3 mmol) in ether (80 mL) and CH2Cl2 (20 mL) under nitrogen. The reaction was completed 30 minutes after the addition. The mixture was poured into a cold aqueous N...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Primary halide
null
null
c1cccc2[nH]ccc12
HBr
C(Cl)Cl.CCOCC
null
0.5
BrP(Br)Br.CC(C)(C)OC(=O)n1ccc2c(CO)cccc21>C(Cl)Cl.CCOCC>CC(C)(C)OC(=O)n1ccc2c(CBr)cccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7e08ad6461e04781b376d6f3d0f83053
CC(C)(C)OC(=O)N1CCC(C=O)C1>>C=CC1CCN(C(=O)OC(C)(C)C)C1
C(C)(C)(C)OC(=O)N1CC(CC1)C=O.C(CCC)[Li].[Br-].C1(=CC=CC=C1)C(C1=CC=CC=C1)(C1=CC=CC=C1)[PH3+].[Cl-].[NH4+]>>C(C)(C)(C)OC(=O)N1CC(CC1)C=C
O=[CH:2][CH:3]1[CH2:4][CH2:5][N:6]([C:7](=[O:8])[O:9][C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14]1>>[CH2:1]=[CH:2][CH:3]1[CH2:4][CH2:5][N:6]([C:7](=[O:8])[O:9][C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14]1
CC(C)(C)OC(=O)N1CCC(C=O)C1
C=CC1CCN(C(=O)OC(C)(C)C)C1
null
null
C(C)(=O)OCC.O1CCCC1.CCCCCC
Functional Group Interconversion
OtherReaction
dd6fb167b4e71f3ea190d18ad4e87d18c641d879b83b47beb9dc06bc791584b1
6b3ec9b506a5bb4882685e77a1e07fcb518f891061dfbc2d36767289330c841e
C1CCNC1
O=[CH;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5]>>[#7:5]-[C:4]-[C:2](-[CH;D2;+0:1]=[C;D1;H2:6])-[C:3]
89.7
[{"value": 89.7, "product": "C(C)(C)(C)OC(=O)N1CC(CC1)C=C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
0.5
HOUR
n-Butyllithium in hexane (44 cm3 of a 1.6 N solution) was added drop-wise to a suspension of 25.5 g (71 mmol) of triphenylmethylphosphonium bromide in 300 cm3 of tetrahydrofuran, which was under argon and cooled to 0° C. The reaction mixture was stirred at 0° C. for 0.5 h and then admixed with a solution of 7.1 g (35.6...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Vinyl
null
null
C1CC[NH]C1
null
C(C)(=O)OCC.O1CCCC1.CCCCCC
0
0.5
CC(C)(C)OC(=O)N1CCC(C=O)C1>C(C)(=O)OCC.O1CCCC1.CCCCCC>C=CC1CCN(C(=O)OC(C)(C)C)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ada3a438f89c4bfbbbdb163094b9a1cc
NCCC1=CC=C(O)C(O)C1>>NCCc1ccc(O)c(O)c1
NCCC=1CC(O)C(O)=CC1.N1=CC=CC(=C1)C1N(C)CCC1>>NCCC1=CC(O)=C(O)C=C1
[NH2:1][CH2:2][CH2:3][C:4]1=[CH:5][CH:6]=[C:7]([OH:8])[CH:9]([OH:10])[CH2:11]1>>[NH2:1][CH2:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([OH:8])[c:9]([OH:10])[cH:11]1
NCCC1=CC=C(O)C(O)C1
NCCc1ccc(O)c(O)c1
null
null
null
Miscellaneous
OtherReaction
d72dc877dbda7d080b263ebc2b8cd165e38d60ff56a667714eb8e3aa080aed81
ef49430386e4c58f0f103ac84bb7f8be7a7fcba093512db68d8ff45186c8f6c2
c1ccccc1
[C:1]-[C:2]-[C;H0;D3;+0:3]1=[CH;D2;+0:4]-[CH;D2;+0:5]=[C;H0;D3;+0:6](-[O;D1;H1:7])-[CH;D3;+0:8](-[O;D1;H1:9])-[CH2;D2;+0:10]-1>>[C:1]-[C:2]-[c;H0;D3;+0:3]1:[cH;D2;+0:10]:[c;H0;D3;+0:8](-[O;D1;H1:9]):[c;H0;D3;+0:6](-[O;D1;H1:7]):[cH;D2;+0:5]:[cH;D2;+0:4]:1
null
[]
null
null
10
MINUTE
The synaptosomal suspension was incubated for 10 minutes at 37° C. to restore metabolic activity. [3H]Dopamine ([3H]DA, specific activity=28.0 Ci/mmol, NEN Research Products) was added at a final concentration of 0.1 μM and the suspension was incubated at 37° C. for another 10 minutes. 50 μL aliquots of tissue +100 μL ...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Enol.Conjugated diene
Aromatic alcohol.Aromatic alcohol
C1=CCCC=C1
c1ccccc1
c1ccccc1
null
null
null
0.166667
NCCC1=CC=C(O)C(O)C1>>NCCc1ccc(O)c(O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-328e756752e84921bd9155ec1c1ac88c
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1.Clc1nc(Cl)c2ccnc-2[nH]1>>Clc1nc(-c2ccco2)c2ccnc-2[nH]1
ClC1=NC(=C2C(N1)=NC=C2)Cl.C(CCC)[Sn](C=1OC=CC1)(CCCC)CCCC>>ClC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c:5]1[cH:6][cH:7][cH:8][o:9]1.Cl[c:4]1[n:3][c:2]([Cl:1])[nH:15][c:14]2[n:13][cH:12][cH:11][c:10]1-2>>[Cl:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][cH:8][o:9]2)[c:10]2[cH:11][cH:12][n:13][c:14]-2[nH:15]1
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1.Clc1nc(Cl)c2ccnc-2[nH]1
Clc1nc(-c2ccco2)c2ccnc-2[nH]1
null
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl
C(C)OCC.CN(C)C=O
C-C Coupling
Stille reaction_aryl
6aa8c09d3c0407c9aaf6499bf289fd57fe4b1f52b9fee773c7ce50acce18771d
db27eeefac0475c6d74fa10b3167e95a61caaae74e8bbafd45892452c0c3d4d6
c1coc(-c2nc[nH]c3nccc2-3)c1
C-C-C-[CH2]-[Sn](-[CH2]-C-C-C)(-[CH2]-C-C-C)-[c;H0;D3;+0:1]1:[#8;a:2]:[c:3]:[c:4]:[c:5]:1.Cl-[c;H0;D3;+0:6]1:[#7;a:7]:[c:8]:[#7;a:9]:[c:10]2:[#7;a:11]:[c:12]:[c:13]:[c:14]:1-2>>[#7;a:11]1:[c:12]:[c:13]:[c:14]2:[c;H0;D3;+0:6](-[c;H0;D3;+0:1]3:[#8;a:2]:[c:3]:[c:4]:[c:5]:3):[#7;a:7]:[c:8]:[#7;a:9]:[c:10]:1-2
61.4
[{"value": 61.0, "product": "ClC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.4, "product": "ClC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A solution of 2,4-dichloro-1H-pyrrolo[2,3-d]pyrimidine (4.1 g, 21.8 mmol) in DMF (20 mL) was treated with PdCl2(PPh3)2 (772 mg, 0.17 mmol) and 2-(tributylstannyl)-furan (6.9 mL, 21.8 mmol), stirred at room temperature for 16 h, diluted with diethyl ether and filtered to give the title compound (2.94 g, 61%) as a pale o...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
null
c1ccoc1.c1ncc2cc[nH]c2n1
c1ccoc1.c1ncc2cc[nH]c2n1
c1ccoc1.c1ncc2cc[nH]c2n1
HCl.Sn
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.C(C)OCC.CN(C)C=O
null
16
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccco1.Clc1nc(Cl)c2ccnc-2[nH]1>Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.C(C)OCC.CN(C)C=O>Clc1nc(-c2ccco2)c2ccnc-2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-13d810c18f0c45ee97e9e518ee55d635
Clc1nc(-c2ccco2)c2ccnc-2[nH]1.Fc1ccccc1CBr>>Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21
FC1=C(CBr)C=CC=C1.ClC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2.[H-].[Na+]>>ClC=1N=C(C2=C(N1)N(C=C2)CC2=C(C=CC=C2)F)C=2OC=CC2
[n:9]1[cH:10][cH:11][c:12]2[c:13](-[c:14]3[cH:15][cH:16][cH:17][o:18]3)[n:19][c:20]([Cl:21])[nH:22][c:23]1-2.Br[CH2:8][c:7]1[c:2]([F:1])[cH:3][cH:4][cH:5][cH:6]1>>[F:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1[CH2:8][n:9]1[cH:10][cH:11][c:12]2[c:13](-[c:14]3[cH:15][cH:16][cH:17][o:18]3)[n:19][c:20]([Cl:21])[n:22][c:23]12
Clc1nc(-c2ccco2)c2ccnc-2[nH]1.Fc1ccccc1CBr
Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
edd5857a15d7b36c5d4505944cd0264d067ed458a95f422fadba87dda59a933b
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(Cn2ccc3c(-c4ccco4)ncnc32)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#8;a:5]:[c:6]-[c:7]1:[#7;a:8]:[c:9](-[Cl;D1;H0:10]):[nH;D2;+0:11]:[c;H0;D3;+0:12]2:[n;H0;D2;+0:13]:[c:14]:[c:15]:[c;H0;D3;+0:16]:1-2>>[#8;a:5]:[c:6]-[c:7]1:[#7;a:8]:[c:9](-[Cl;D1;H0:10]):[n;H0;D2;+0:11]:[c;H0;D3;+0:12]2:[c;H0;D3;+0:16]:1:[c:15]:[c:14]:[n;H0;D3;+0:13]:2-[CH2;D2;+0:1...
76.3
[{"value": 76.0, "product": "ClC=1N=C(C2=C(N1)N(C=C2)CC2=C(C=CC=C2)F)C=2OC=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.3, "product": "ClC=1N=C(C2=C(N1)N(C=C2)CC2=C(C=CC=C2)F)C=2OC=CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
A solution of 2-chloro-4-(2-furyl)-1H-pyrrolo[2,3-d]pyrimidine (219 mg, 1 mmol) in DMF (2 mL) at 0° C. was treated with NaH (40 mg, 60%, 1 mmol), stirred for 20 min, treated with 2-fluorobenzyl bromide (120 μL, 1 mmol), stirred at room temperature for 1 h, quenched with water, extracted with EtOAc, dried (MgSO4), conce...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
c1ccccc1.c1ccoc1.c1ncc2cc[nH]c2n1
HBr
CN(C)C=O
null
0.333333
Clc1nc(-c2ccco2)c2ccnc-2[nH]1.Fc1ccccc1CBr>CN(C)C=O>Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-24ae2260c3ff44c886402ed1bd64b0dd
COc1ccc(CN)cc1OC.Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21>>COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC
ClC=1N=C(C2=C(N1)N(C=C2)CC2=C(C=CC=C2)F)C=2OC=CC2.C(C1=CC(OC)=C(OC)C=C1)N>>COC=1C=C(CNC=2N=C(C3=C(N2)N(C=C3)CC3=C(C=CC=C3)F)C=3OC=CC3)C=CC1OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][NH2:8])[cH:31][c:32]1[O:33][CH3:34].Cl[c:9]1[n:10][c:11](-[c:12]2[cH:13][cH:14][cH:15][o:16]2)[c:17]2[cH:18][cH:19][n:20]([CH2:21][c:22]3[cH:23][cH:24][cH:25][cH:26][c:27]3[F:28])[c:29]2[n:30]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][NH:8][c:9]2[n:10][c:11](-[c:12]3[cH:1...
COc1ccc(CN)cc1OC.Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21
COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC
null
null
CN1C(CCC1)=O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
7d8cc6c05eda9dfa6bdabe6a29061e2976ad8c7049d801bee87af917df08c113
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4)c3n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5](:[#7;a:6]:1):[#7;a:7](-[C:8]):[c:9].[NH2;D1;+0:10]-[C:11]-[c:12]>>[C:8]-[#7;a:7](:[c:9]):[c:5]1:[#7;a:6]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C:11]-[c:12]):[#7;a:2]:[c:3]:[c:4]:1
88.4
[{"value": 88.0, "product": "COC=1C=C(CNC=2N=C(C3=C(N2)N(C=C3)CC3=C(C=CC=C3)F)C=3OC=CC3)C=CC1OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.4, "product": "COC=1C=C(CNC=2N=C(C3=C(N2)N(C=C3)CC3=C(C=CC=C3)F)C=3OC=CC3)C=CC1OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A solution of 2-chloro-7-(2-fluorobenzyl)4(2-furyl)-7H-pyrrolo[2,3-d]pyrimidine (254 mg, 0.78 mmol) in N-methylpyrrolidone (2 mL) was treated with veratrylamine (0.25 mL, 1.66 mmol), heated to 100° C. for 16 h and purified by chromatography (Heptane:EtOAc, 4:1) to give the title compound (316 mg, 88%) as a cream solid....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
c1ccccc1.c1ccoc1.c1ncc2cc[nH]c2n1.c1ccccc1
HCl
CN1C(CCC1)=O
100
null
COc1ccc(CN)cc1OC.Fc1ccccc1Cn1ccc2c(-c3ccco3)nc(Cl)nc21>CN1C(CCC1)=O>COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-33bf0de3f8aa48d1816747caea2ecde9
COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC>>Nc1nc(-c2ccco2)c2ccn(Cc3ccccc3F)c2n1
COC=1C=C(CNC=2N=C(C3=C(N2)N(C=C3)CC3=C(C=CC=C3)F)C=3OC=CC3)C=CC1OC>>FC1=C(CN2C=CC3=C2N=C(N=C3C=3OC=CC3)N)C=CC=C1
COc1ccc(C[NH:1][c:2]2[n:3][c:4](-[c:5]3[cH:6][cH:7][cH:8][o:9]3)[c:10]3[cH:11][cH:12][n:13]([CH2:14][c:15]4[cH:16][cH:17][cH:18][cH:19][c:20]4[F:21])[c:22]3[n:23]2)cc1OC>>[NH2:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][cH:8][o:9]2)[c:10]2[cH:11][cH:12][n:13]([CH2:14][c:15]3[cH:16][cH:17][cH:18][cH:19][c:20]3[F:21])[c:22]2[...
COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC
Nc1nc(-c2ccco2)c2ccn(Cc3ccccc3F)c2n1
null
null
C(=O)(C(F)(F)F)O
Reduction
OtherReaction
93295f0bc4e4cc47e665b12bc7fe58c9728c9fb915c15424d06f1616b6912002
9fb4bdd681eea7aeb7e37bbfb0aa4538a773561d0c8ffc2bcfecd748c2197589
c1ccc(Cn2ccc3c(-c4ccco4)ncnc32)cc1
C-O-c1:c:c:c(-C-[NH;D2;+0:1]-[c:2](:[#7;a:3]:[c:4]:[#7;a:5]):[#7;a:6]:[c:7]):c:c:1-O-C>>[#7;a:5]:[c:4]:[#7;a:3]:[c:2](-[NH2;D1;+0:1]):[#7;a:6]:[c:7]
51.4
[{"value": 51.0, "product": "FC1=C(CN2C=CC3=C2N=C(N=C3C=3OC=CC3)N)C=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.4, "product": "FC1=C(CN2C=CC3=C2N=C(N=C3C=3OC=CC3)N)C=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of N-(3,4-dimethoxybenzyl)-7-(2-fluorobenzyl)4-(2-furyl)-7H-pyrrolo[2,3-d]pyrimidine-2-amine (110 mg, 0.24 mmol) in TFA (1 mL) was heated to 50° C. for 3 h, concentrated in vacuo, treated with saturated NaHCO3, extracted with EtOAc, dried (MgSO4), concentrated in vacuo, purified by chromatography (EtOAc:Hept...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Secondary amine
Primary amine
c1ccccc1
null
c1ccoc1.c1ncc2cc[nH]c2n1.c1ccccc1
HO-
C(=O)(C(F)(F)F)O
null
null
COc1ccc(CNc2nc(-c3ccco3)c3ccn(Cc4ccccc4F)c3n2)cc1OC>C(=O)(C(F)(F)F)O>Nc1nc(-c2ccco2)c2ccn(Cc3ccccc3F)c2n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a071ae83731e44dba70337a8f6a9c26b
CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1.O=C(Cl)c1ccccc1>>CN(C)c1nc(-c2ccco2)c2ccn(C(=O)c3ccccc3)c2n1
CN(C1=NC(=C2C(N1)=NC=C2)C=2OC=CC2)C.CCN(CC)CC.C(C1=CC=CC=C1)(=O)Cl>>C(C1=CC=CC=C1)(=O)N1C=CC2=C1N=C(N=C2C=2OC=CC2)N(C)C
[CH3:1][N:2]([CH3:3])[c:4]1[n:5][c:6](-[c:7]2[cH:8][cH:9][cH:10][o:11]2)[c:12]2[cH:13][cH:14][n:15][c:24]-2[nH:25]1.Cl[C:16](=[O:17])[c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1>>[CH3:1][N:2]([CH3:3])[c:4]1[n:5][c:6](-[c:7]2[cH:8][cH:9][cH:10][o:11]2)[c:12]2[cH:13][cH:14][n:15]([C:16](=[O:17])[c:18]3[cH:19][cH:20][cH:21...
CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1.O=C(Cl)c1ccccc1
CN(C)c1nc(-c2ccco2)c2ccn(C(=O)c3ccccc3)c2n1
null
CN(C)C=1C=CN=CC1
C1CCOC1
Acylation
OtherReaction
138010d210cab22bc5a9617aec89dab5412792532bc7ffbfd582354a2e40c660
edbcca52d877d662e04f0d6de1a7107a8eca1d366ee6da0d92e37eb02a291876
O=C(c1ccccc1)n1ccc2c(-c3ccco3)ncnc21
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#7:6]-[c:7]1:[#7;a:8]:[c:9](-[c:10]:[#8;a:11]):[c;H0;D3;+0:12]2:[c:13]:[c:14]:[n;H0;D2;+0:15]:[c;H0;D3;+0:16]-2:[nH;D2;+0:17]:1>>[#7:6]-[c:7]1:[#7;a:8]:[c:9](-[c:10]:[#8;a:11]):[c;H0;D3;+0:12]2:[c:13]:[c:14]:[n;H0;D3;+0:15](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4])...
28.6
[{"value": 28.6, "product": "C(C1=CC=CC=C1)(=O)N1C=CC2=C1N=C(N=C2C=2OC=CC2)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of N,N-dimethyl-4-(2-furyl)-1H-pyrrolo[2,3-d]pyrimidine-2-amine (181 mg, 0.8 mmol) in THF (3 mL) was treated with Et3N, (111 μL, 0.8 mmol), benzoyl chloride (93 μL, 0.8 mmol) and a catalytic amount of DMAP, stirred at room temperature for 16 h, quenched with water, extracted with EtOAc, dried (MgSO4), concen...
10.6084/m9.figshare.5104873.v1
null
Acyl halide
null
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
c1ccoc1.c1ncc2cc[nH]c2n1.c1ccccc1
HCl
CN(C)C=1C=CN=CC1.C1CCOC1
null
null
CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1.O=C(Cl)c1ccccc1>CN(C)C=1C=CN=CC1.C1CCOC1>CN(C)c1nc(-c2ccco2)c2ccn(C(=O)c3ccccc3)c2n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e3a6e51d909246489019c19083530959
Nc1nc(-c2ccco2)c2ccnc-2[nH]1.O=C=NCc1ccccc1>>O=C(NCc1ccccc1)Nc1nc(-c2ccco2)c2ccnc-2[nH]1
O1C(=CC=C1)C1=C2C(NC(=N1)N)=NC=C2.C(C1=CC=CC=C1)N=C=O>>C(C1=CC=CC=C1)NC(=O)NC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2
[NH2:11][c:12]1[n:13][c:14](-[c:15]2[cH:16][cH:17][cH:18][o:19]2)[c:20]2[cH:21][cH:22][n:23][c:24]-2[nH:25]1.[O:1]=[C:2]=[N:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1>>[O:1]=[C:2]([NH:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1)[NH:11][c:12]1[n:13][c:14](-[c:15]2[cH:16][cH:17][cH:18][o:19]2)[c:20]2[cH:21][cH:2...
Nc1nc(-c2ccco2)c2ccnc-2[nH]1.O=C=NCc1ccccc1
O=C(NCc1ccccc1)Nc1nc(-c2ccco2)c2ccnc-2[nH]1
null
null
C1CCOC1
Acylation
Urea synthesis via isocyanate and primary amine
d39cd7dc52a79bb265ff8ef61ef7bf9dc7f7b5fb0150fcb4881bdfb18ab9c380
a5dc801930c765d2a435a0a2973e50163c305ba8e7641d6adbcc1550b7b96de7
O=C(NCc1ccccc1)Nc1nc(-c2ccco2)c2ccnc-2[nH]1
[#7;a:1]:[c:2]:[#7;a:3]:[c:4](-[NH2;D1;+0:5]):[#7;a:6]:[c:7].[O;D1;H0:8]=[C;H0;D2;+0:9]=[N;H0;D2;+0:10]-[C:11]-[c:12]>>[#7;a:1]:[c:2]:[#7;a:3]:[c:4](-[NH;D2;+0:5]-[C;H0;D3;+0:9](=[O;D1;H0:8])-[NH;D2;+0:10]-[C:11]-[c:12]):[#7;a:6]:[c:7]
19.1
[{"value": 19.0, "product": "C(C1=CC=CC=C1)NC(=O)NC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 19.1, "product": "C(C1=CC=CC=C1)NC(=O)NC1=NC(=C2C(N1)=NC=C2)C=2OC=CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A solution of 4-(2-furyl)-1H-pyrrolo[2,3-d]pyrimidine-2-amine (192 mg, 0.96 mmol) in THF (3 mL) was treated with benzyl isocyanate (118 μL, 0.96 mmol), stirred at room temperature for 16 h and the resulting solid filtered and washed with EtOAc to give the title compound (61 mg, 19%) as a yellow solid. Conditions: See r...
10.6084/m9.figshare.5104873.v1
null
Isocyanate.Primary amine
Urea
null
null
c1ccccc1.c1ccoc1.c1ncc2cc[nH]c2n1
null
C1CCOC1
null
16
Nc1nc(-c2ccco2)c2ccnc-2[nH]1.O=C=NCc1ccccc1>C1CCOC1>O=C(NCc1ccccc1)Nc1nc(-c2ccco2)c2ccnc-2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4602b66e6fc3458f9668186fafd743ef
C[Si](C)(C)CCCl.Clc1nc(Cl)c2ccnc-2[nH]1.O>>C[Si](C)(C)CCOCn1ccc2c(Cl)nc(Cl)nc21
O.C[Si](C)(C)CCCl.ClC1=NC(=C2C(N1)=NC=C2)Cl.[H-].[Na+].CC#N>>ClC=1N=C(C2=C(N1)N(C=C2)COCC[Si](C)(C)C)Cl
Cl[CH2:6][CH2:5][Si:2]([CH3:1])([CH3:3])[CH3:4].[n:9]1[cH:10][cH:11][c:12]2[c:13]([Cl:14])[n:15][c:16]([Cl:17])[nH:18][c:19]1-2.[OH2:7]>>[CH3:1][Si:2]([CH3:3])([CH3:4])[CH2:5][CH2:6][O:7][CH2:8][n:9]1[cH:10][cH:11][c:12]2[c:13]([Cl:14])[n:15][c:16]([Cl:17])[n:18][c:19]12
C[Si](C)(C)CCCl.Clc1nc(Cl)c2ccnc-2[nH]1.O
C[Si](C)(C)CCOCn1ccc2c(Cl)nc(Cl)nc21
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
67c2afc52a9de03aa4479dd8b8b7a3e2e5f335bb0c6d666cea4c2e8ad04772f8
62c7c72c35b09d63ca1131e6cd8c0b88a31e29901d660456b77319cfd78354c7
c1ncc2cc[nH]c2n1
Cl-[CH2;D2;+0:1]-[C:2]-[#14:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[C;D1;H3:6].[Cl;D1;H0:7]-[c:8]1:[#7;a:9]:[c:10](-[Cl;D1;H0:11]):[nH;D2;+0:12]:[c;H0;D3;+0:13]2:[n;H0;D2;+0:14]:[c:15]:[c:16]:[c;H0;D3;+0:17]:1-2.[OH2;D0;+0:18]>>[C;D1;H3:4]-[#14:3](-[C;D1;H3:5])(-[C;D1;H3:6])-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:18]-[C:19]-[n;H0;D3;...
104
[{"value": 104.0, "product": "ClC=1N=C(C2=C(N1)N(C=C2)COCC[Si](C)(C)C)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 2,4-dichloro-1H-pyrrolo[2,3-d]pyrimidine (542 mg, 2.58 mmol) in MeCN (20 mL) was treated with NaH (113 mg, 2.84 mmol), stirred for 1 h, treated with trimethylsilylethyl chloride (502 μL, 2.84 mmol), stirred at room temperature for 3 h, poured into water, extracted with EtOAc, dried (MgSO4) and concentrate...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Ether
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
null
null
null
1
C[Si](C)(C)CCCl.Clc1nc(Cl)c2ccnc-2[nH]1.O>>C[Si](C)(C)CCOCn1ccc2c(Cl)nc(Cl)nc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7c74cc044148410e80873354e55e0c9e
CN(C)c1nc(-c2ccco2)c2ccn(COCC[Si](C)(C)C)c2n1>>CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1
O.CN(C=1N=C(C2=C(N1)N(C=C2)COCC[Si](C)(C)C)C=2OC=CC2)C.[F-].C(CCC)[N+](CCCC)(CCCC)CCCC>>CN(C1=NC(=C2C(N1)=NC=C2)C=2OC=CC2)C
C[Si](C)(C)CCOC[n:15]1[cH:14][cH:13][c:12]2[c:6](-[c:7]3[cH:8][cH:9][cH:10][o:11]3)[n:5][c:4]([N:2]([CH3:1])[CH3:3])[n:17][c:16]21>>[CH3:1][N:2]([CH3:3])[c:4]1[n:5][c:6](-[c:7]2[cH:8][cH:9][cH:10][o:11]2)[c:12]2[cH:13][cH:14][n:15][c:16]-2[nH:17]1
CN(C)c1nc(-c2ccco2)c2ccn(COCC[Si](C)(C)C)c2n1
CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1
null
null
C1CCOC1
Reduction
OtherReaction
d7eb80c127bc5b6eb101f8e75644fc9947e9bb2ac217b88e4a795e634b7003a3
d646edd3b1165ce8eea24b0587d24c565cf6371928b4879100704e7b3cd85ed9
c1coc(-c2nc[nH]c3nccc2-3)c1
C-[Si](-C)(-C)-C-C-O-C-[n;H0;D3;+0:1]1:[c:2]:[c:3]:[c;H0;D3;+0:4]2:[c:5](-[c:6]:[#8;a:7]):[#7;a:8]:[c:9](-[#7:10]):[n;H0;D2;+0:11]:[c;H0;D3;+0:12]:2:1>>[#7:10]-[c:9]1:[#7;a:8]:[c:5](-[c:6]:[#8;a:7]):[c;H0;D3;+0:4]2:[c:3]:[c:2]:[n;H0;D2;+0:1]:[c;H0;D3;+0:12]-2:[nH;D2;+0:11]:1
21.2
[{"value": 21.0, "product": "CN(C1=NC(=C2C(N1)=NC=C2)C=2OC=CC2)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 21.2, "product": "CN(C1=NC(=C2C(N1)=NC=C2)C=2OC=CC2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of N,N-dimethyl4-(2-furyl)-7-(2-trimethylsilylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-amine (370 mg, 0.97 mmol) in THF (3 mL) was treated with tetrabutylammonium fluoride (1 ml, 1-M in THF, 1 mmol), refluxed for 36 h, poured into water, extracted with EtOAc, dried (MgSO4), concentrated in vacuo and purif...
10.6084/m9.figshare.5104873.v1
null
Ether.Silyl protective group
null
c1ncc2cc[nH]c2n1
c1ncc2cc[nH]c2n1
c1ccoc1.c1ncc2cc[nH]c2n1
HO-
C1CCOC1
null
null
CN(C)c1nc(-c2ccco2)c2ccn(COCC[Si](C)(C)C)c2n1>C1CCOC1>CN(C)c1nc(-c2ccco2)c2ccnc-2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-91a500af0c324fcda1988389295dd3f8
CC(=O)c1ccccc1>>O=C(C=Cc1ccccc1)c1ccccc1
C[O-].[Na+].C(C)(=O)C1=CC=CC=C1>>C1(=CC=CC=C1)C=CC(=O)C1=CC=CC=C1
[O:1]=[C:2]([CH3:3])[c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1>>[O:1]=[C:2]([CH:3]=[CH:4][c:5]1[cH:6][cH:7][cH:8][cH:9][cH:10]1)[c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1
CC(=O)c1ccccc1
O=C(C=Cc1ccccc1)c1ccccc1
null
null
C1CCOC1.CO
C-C Coupling
OtherReaction
56c4f02478b08d261cea23de43f494776c78ec679e7e270a5eda4662f054aad8
6c72a64362b644ff7380f8d0c7bdda962edffb1f22535d7f0916fcd367b6b992
O=C(C=Cc1ccccc1)c1ccccc1
[CH3;D1;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[c:4])-[CH;D2;+0:1]=[C:5]-[c:6]
null
[]
null
null
3
DAY
Reaction of Aldehydes with Wang Resin-bound Acetophenones: Each packet of Acetophenone-Wang resin was transferred to a 250 mL PP bottle, to which a solution of NaOMe (51.2 mmol, 20 eq, 0.25 M) in 50% THF-MeOH (205 mL) and an aldehyde (51.2 mmol, 20 eq, 0.25 M) were added sequentially. After shaking at room temperature ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Ketone
null
c1ccccc1
c1ccccc1.c1ccccc1
Other
C1CCOC1.CO
null
72
CC(=O)c1ccccc1>C1CCOC1.CO>O=C(C=Cc1ccccc1)c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-058e86fe19104b3e93276368ff9bb7d7
C=O.O=c1cc[nH]c(=O)[nH]1>>O=c1[nH]cc(CO)c(=O)[nH]1
[OH-].[K+].Cl.NO.N1C(=O)NC(=O)C=C1.C=O>>OCC=1C(NC(NC1)=O)=O
[CH2:6]=[O:7].[O:1]=[c:2]1[nH:3][cH:4][cH:5][c:8](=[O:9])[nH:10]1>>[O:1]=[c:2]1[nH:3][cH:4][c:5]([CH2:6][OH:7])[c:8](=[O:9])[nH:10]1
C=O.O=c1cc[nH]c(=O)[nH]1
O=c1[nH]cc(CO)c(=O)[nH]1
null
null
O
C-C Coupling
OtherReaction
67448c64d4a30a61f5e502af4acf85fb4cc3d0f5db899aa52bfc35f9dce8fff1
4396295d899f5d4f5de2e844a80fc7d194b4da158f49df3d2717206b401b59bd
O=c1cc[nH]c(=O)[nH]1
[CH2;D1;+0:1]=[O;H0;D1;+0:2].[O;D1;H0:3]=[c:4]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:[cH;D2;+0:9]:1>>[O;D1;H0:3]=[c:4]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:[c;H0;D3;+0:9]:1-[CH2;D2;+0:1]-[OH;D1;+0:2]
14.5
[{"value": 14.5, "product": "OCC=1C(NC(NC1)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
68
HOUR
A 2-L, three-necked flask equipped with a mechanical stirrer, thermometer, condenser, and nitrogen-inlet bubbler was charged with uracil (185.0 g, 1650 mmol) (Aldrich), paraformaldehyde (61.50 g, 2050 mmol as formaldehyde) (Aldrich), and a solution of potassium hydroxide (86.9%, 59.95 g, 928.5 mmol) (Aldrich) in water ...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde
Primary alcohol
c1ccncn1
c1cncnc1
c1cncnc1
null
O
null
68
C=O.O=c1cc[nH]c(=O)[nH]1>O>O=c1[nH]cc(CO)c(=O)[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c65460f7404d4c359602cdb11f0d47b8
ClCc1cnc(Cl)nc1Cl.[I-]>>Clc1ncc(CI)c(Cl)n1
[I-].[Na+].ClC1=NC=C(C(=N1)Cl)CCl>>ClC1=NC=C(C(=N1)Cl)CI
Cl[CH2:6][c:5]1[cH:4][n:3][c:2]([Cl:1])[n:10][c:8]1[Cl:9].[I-:7]>>[Cl:1][c:2]1[n:3][cH:4][c:5]([CH2:6][I:7])[c:8]([Cl:9])[n:10]1
ClCc1cnc(Cl)nc1Cl.[I-]
Clc1ncc(CI)c(Cl)n1
null
null
CC(=O)C
Functional Group Interconversion
OtherReaction
e944a2acb95a43a23818321f2ac2f96ba2f2b8d34f52c1cfd1e3802d2403177f
e2ca6f9fe1078a3836d617896a4e5cc310fb155ca459b021e2b549b3e61f1df7
c1cncnc1
Cl-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[I-;H0;D0:9]>>[Cl;D1;H0:8]-[c:7]1:[#7;a:6]:[c:5]:[#7;a:4]:[c:3]:[c:2]:1-[CH2;D2;+0:1]-[I;H0;D1;+0:9]
null
[]
null
null
20
MINUTE
A 500-mL, round-bottom flask equipped with a magnetic stirrer, condenser, and nitrogen-inlet bubbler was charged with sodium iodide (38.5 g, 256.9 mmol) (Aldrich) and acetone (300 mL). After a clear solution was obtained, 2,4-dichloro-5-(chloromethyl)pyrimidine (50.0 g, 253.2 mmol) (from Example 1b supra) was added in ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Primary halide
null
null
c1cncnc1
Other
CC(=O)C
null
0.333333
ClCc1cnc(Cl)nc1Cl.[I-]>CC(=O)C>Clc1ncc(CI)c(Cl)n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1f20269900804e01908b99c9d221b00d
COC(=O)Cc1ccc(OC)cc1.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1
ClC1=NC=C(C(=N1)Cl)CI.COC(CC1=CC=C(C=C1)OC)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=C(C=C1)OC)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[cH:16][cH:17][c:18]([O:19][CH3:20])[cH:21][cH:22]1.I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[cH:16][cH:17][c:18]([O:19][CH3:20])[cH:21][cH:22]1
COC(=O)Cc1ccc(OC)cc1.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (720 mg, 5.0 mmol) (Aldrich) in dry tetrahydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2.0 mL, 5.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 4-methoxyphenylacetic acid methyl ester (900 mg, 5.0 mmol) (Aldrich) in tetrahydrofuran ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
COC(=O)Cc1ccc(OC)cc1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4afc1eb06a12450d987aa3451652d5af
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=C(C=C1)OC)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC=C(C=C1)OC)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[cH:28][cH:29][c:30]([O:31][CH3:32])[cH:33][cH:34]2)[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18][c:1...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]):[c:6]:[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:2]:[c;H0;D3;+0:3]:1-[#7:12]-[c:13]
null
[]
110
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (0.54 g, 1.58 mmol) (from Example 1d supra) and aniline (0.67 g, 7.11 mmol) (Aldrich) was heated at 110° C. for 30 minutes. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
110
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-72569249a4644535976a717f79b97131
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC=C(C=C1)OC)=O.S(O)(O)(=O)=O>>COC1=CC=C(C=C1)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CO[C:29]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:32][cH:31]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[n:20][c:21]1[NH:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1)=[O:30]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([NH:13][c:14]4[cH:...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1
COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
80
CELSIUS
null
null
To the solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (227.3 mg, 0.5 mmol) (from Example 1e supra) in glacial acetic acid (15 mL) was added concentrated sulfuric acid (0.2 mL) in one portion. The reaction mixture was heated at 80° C. overnight. The reaction mixture was...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
80
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)cc1>C(C)(=O)O.C(C)(=O)OCC>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c522ce02ad534b87ac0c7d472d464fbf
COC(=O)Cc1c(Cl)cccc1Cl.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl
COC(CC1=C(C=CC=C1Cl)Cl)=O.ClC1=NC=C(C(=N1)Cl)CI.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC=C1Cl)Cl)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[c:16]([Cl:17])[cH:18][cH:19][cH:20][c:21]1[Cl:22].I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[c:16]([Cl:17])[cH:18][cH:19][cH:20][c:21]1[Cl:22]
COC(=O)Cc1c(Cl)cccc1Cl.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2,6-dichloro-phenylacetic acid methyl ester (2.19 g, 10.0 mmol) (TCI-US) in tetrahydro...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
COC(=O)Cc1c(Cl)cccc1Cl.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a348e451808443f4981f4358045c1ae5
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC=C1Cl)Cl)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=C(C=CC=C1Cl)Cl)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[c:28]([Cl:29])[cH:30][cH:31][cH:21][c:33]2[Cl:34])[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18][c:19...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl
null
null
null
Aromatic Heterocycle Formation
OtherReaction
5915cc0a526f64cbddc143c41954b5b125975e4d919e164608d5a11a413b76fc
45ae7d7d2972e3a9d0ff628eb6c7e0cac8c3e39c85da29f5c6439797c3fe97a5
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]-[C:6](-[C:7](-[#8:8])=[O;D1;H0:9])-[c:10]2:[c:11]:[c:12]:[cH;D2;+0:13]:[cH;D2;+0:14]:[c;H0;D3;+0:15]:2-[Cl;D1;H0:16]):[c:17]:[#7;a:18]:1.[NH2;D1;+0:19]-[c:20](:[c:21]):[c:22]>>[#8:8]-[C:7](=[O;D1;H0:9])-[C:6](-[C:5]-[c:4]1:[c:17]:[#7;a:18]:[c;H0;D3;+0:1](-[NH...
null
[]
110
CELSIUS
null
null
A mixture of 2-(2,6-dichloro-phenyl)-3-(2,4-dichloro-pyrimidin-5-yl)-propionic acid methyl ester (0.20 g, 0.53 mmol) (from Example 2a supra) and aniline (2.0 ml) (Aldrich) was heated at 110° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Primary amine
Aromatic halide.Secondary amine.Secondary amine
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
110
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1c(Cl)cccc1Cl.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2ff6d305ccb84e36a219e0e4e3c0ef09
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl>>O=C1C(c2c(Cl)cccc2Cl)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=C(C=CC=C1Cl)Cl)=O.S(O)(O)(=O)=O>>ClC1=C(C(=CC=C1)Cl)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CO[C:2](=[O:1])[CH:3]([c:4]1[c:5]([Cl:6])[cH:7][cH:8][cH:9][c:10]1[Cl:11])[CH2:12][c:13]1[cH:14][n:15][c:16]([NH:17][c:18]2[cH:19][cH:20][cH:21][cH:22][cH:23]2)[n:24][c:25]1[NH:26][c:27]1[cH:28][cH:29][cH:30][cH:31][cH:32]1>>[O:1]=[C:2]1[CH:3]([c:4]2[c:5]([Cl:6])[cH:7][cH:8][cH:9][c:10]2[Cl:11])[CH2:12][c:13]2[cH:14][n...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl
O=C1C(c2c(Cl)cccc2Cl)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
145
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(2,6-dichloro-phenyl)-propionic acid methyl ester (0.18 g, 0.36 mmol) (from Example 2b supra) in glacial acetic acid (2 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 135° C. overnight and 145° C. for another 4...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
145
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1c(Cl)cccc1Cl>C(C)(=O)O.C(C)(=O)OCC>O=C1C(c2c(Cl)cccc2Cl)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-22aae1a312904b26991097295d0ce830
CO.COc1cc(CC(=O)O)cc(OC)c1>>COC(=O)Cc1cc(OC)cc(OC)c1
COC=1C=C(C=C(C1)OC)CC(=O)O.S(O)(O)(=O)=O.CO>>COC(CC1=CC(=CC(=C1)OC)OC)=O
O[CH3:1].[OH:2][C:3](=[O:4])[CH2:5][c:6]1[cH:7][c:8]([O:9][CH3:10])[cH:11][c:12]([O:13][CH3:14])[cH:15]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:6]1[cH:7][c:8]([O:9][CH3:10])[cH:11][c:12]([O:13][CH3:14])[cH:15]1
CO.COc1cc(CC(=O)O)cc(OC)c1
COC(=O)Cc1cc(OC)cc(OC)c1
null
null
null
Heteroatom Alkylation and Arylation
Esterification of Carboxylic Acids
961bfcd5802efbb4a2d5a1e38cbfb6654b5b78f769c3570df49b858a6f105ab6
0a622556a49b258b9020bd3a5bdd1fa9237e7093cf9b09de3a6b575ffe935dcd
c1ccccc1
O-[CH3;D1;+0:1].[C:2]-[C:3](=[O;D1;H0:4])-[OH;D1;+0:5]>>[C:2]-[C:3](=[O;D1;H0:4])-[O;H0;D2;+0:5]-[CH3;D1;+0:1]
null
[]
null
null
null
null
To a solution of 3,5-dimethoxyphenylacetic acid (1.99 g, 10.0 mmol) (Transworld) in methanol (20 mL) was added concentrated sulfuric acid (1.0 mL) and the reaction mixture was heated at reflux for 24 hours. The reaction mixture was concentrated in vacuo. The residue was then diluted with ethyl acetate (100 mL) and succ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
null
null
null
CO.COc1cc(CC(=O)O)cc(OC)c1>>COC(=O)Cc1cc(OC)cc(OC)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ccebbc825e74486f8f8653f180c27aab
COC(=O)Cc1cc(OC)cc(OC)c1.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1
ClC1=NC=C(C(=N1)Cl)CI.COC(CC1=CC(=CC(=C1)OC)OC)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=CC(=C1)OC)OC)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[cH:16][c:17]([O:18][CH3:19])[cH:20][c:21]([O:22][CH3:23])[cH:24]1.I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[cH:16][c:17]([O:18][CH3:19])[cH:20][c:21]([O:22][CH3...
COC(=O)Cc1cc(OC)cc(OC)c1.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 3,5-dimethoxy-phenyl-acetic acid methyl ester (2.05 g, 9.76 mmol) (from Example 3a sup...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
COC(=O)Cc1cc(OC)cc(OC)c1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0190bb8d43134b739d7eeeeba6f57f89
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=CC(=C1)OC)OC)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=CC(=C1)OC)OC)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[cH:28][c:29]([O:30][CH3:31])[cH:32][c:33]([O:34][CH3:35])[cH:36]2)[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]):[c:6]:[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:2]:[c;H0;D3;+0:3]:1-[#7:12]-[c:13]
null
[]
110
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester (186 mg, 0.50 mmol) (from Example 3b supra) and aniline (2.0 mL) (Aldrich) was heated at 110° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
110
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-71202caef48949bf8ff4e43739e43746
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1>>COc1cc(OC)cc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)c1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=CC(=C1)OC)OC)=O.S(O)(O)(=O)=O.C(C)(=O)O>>COC=1C=C(C=C(C1)OC)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CO[C:32]([CH:10]([c:9]1[cH:8][c:5]([O:6][CH3:7])[cH:4][c:3]([O:2][CH3:1])[cH:34]1)[CH2:11][c:12]1[cH:13][n:14][c:15]([NH:16][c:17]2[cH:18][cH:19][cH:20][cH:21][cH:22]2)[n:23][c:24]1[NH:25][c:26]1[cH:27][cH:28][cH:29][cH:30][cH:31]1)=[O:33]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH3:7])[cH:8][c:9]([CH:10]2[CH2:11][c:12]3[...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1
COc1cc(OC)cc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)c1
null
null
C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
120
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester (0.11 mg, 0.23 mmol) (from Example 3c supra) in glacial acetic acid (2 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 120° C. overnight. The reaction mixture w...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)OCC
120
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1>C(C)(=O)OCC>COc1cc(OC)cc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3047c52f326d4823ad745add3224ef15
COC(=O)Cc1ccccc1.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1
ClC1=NC=C(C(=N1)Cl)CI.COC(CC1=CC=CC=C1)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=CC=C1)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1
COC(=O)Cc1ccccc1.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of phenylacetic acid methyl ester (1.50 g, 10.0 mmol) (Aldrich) in tetrahydrofuran (5 mL)...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
COC(=O)Cc1ccccc1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-52bce4e4c8a344a39a7507d5991567b3
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=CC=C1)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC=CC=C1)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[cH:28][cH:29][cH:30][cH:31][cH:32]2)[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18][c:19]1[NH:20][c:21...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]):[c:6]:[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:2]:[c;H0;D3;+0:3]:1-[#7:12]-[c:13]
null
[]
120
CELSIUS
null
null
The mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-phenyl-propionic acid methyl ester (0.31 g, 1.0 mmol) (from Example 5a supra) and aniline (3.0 mL) (Aldrich) was heated at 120° C. for 1 hour. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The residue was the...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
120
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9da8474bf2d249ce9a1f7b0c9cf31239
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1>>O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC=CC=C1)=O.S(O)(O)(=O)=O>>C1(=CC=CC=C1)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CO[C:2](=[O:1])[CH:3]([c:4]1[cH:5][cH:6][cH:7][cH:8][cH:9]1)[CH2:10][c:11]1[cH:12][n:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][cH:21]2)[n:22][c:23]1[NH:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1>>[O:1]=[C:2]1[CH:3]([c:4]2[cH:5][cH:6][cH:7][cH:8][cH:9]2)[CH2:10][c:11]2[cH:12][n:13][c:14]([NH:15][c:16]3[cH...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
60
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-phenyl-propionic acid methyl ester (100 mg, 0.24 mmol) (from Example 5b supra) was added 5% concentrated sulfuric acid in glacial acetic acid (3 mL) in one portion. The reaction mixture was heated at 60° C. overnight. After cooling, the reaction mixture was dilute...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
60
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1>C(C)(=O)O.C(C)(=O)OCC>O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-dd5c910e75e942149904f05634a4fdcf
CCOC(=O)Cc1cc(OC)ccc1OC.Clc1ncc(CI)c(Cl)n1>>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC
ClC1=NC=C(C(=N1)Cl)CI.C(C)OC(CC1=C(C=CC(=C1)OC)OC)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC(=C1)OC)OC)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:16]1[cH:17][c:18]([O:19][CH3:20])[cH:21][cH:22][c:23]1[O:24][CH3:25].I[CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15])[c:16]1[cH:17][c:18]([O:19][CH3:20])[cH:21][cH...
CCOC(=O)Cc1cc(OC)ccc1OC.Clc1ncc(CI)c(Cl)n1
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2,5-dimethoxyphenylacetic acid ethyl ester (2.24 g, 10.0 mmol) (Aldrich) in tetrahydro...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
CCOC(=O)Cc1cc(OC)ccc1OC.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-19608b27c86f40259bbd4f5626910edb
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC>>CCOC(=O)C(C)c1cc(OC)ccc1OC
C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC(=C1)OC)OC)=O.NC1=CC=CC=C1>>C(C)OC(C(C)C1=C(C=CC(=C1)OC)OC)=O
Clc1ncc([CH2:7][CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:8]2[cH:9][c:10]([O:11][CH3:12])[cH:13][cH:14][c:15]2[O:16][CH3:17])c(Cl)n1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH3:7])[c:8]1[cH:9][c:10]([O:11][CH3:12])[cH:13][cH:14][c:15]1[O:16][CH3:17]
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC
CCOC(=O)C(C)c1cc(OC)ccc1OC
null
null
null
Miscellaneous
OtherReaction
5eb8f6bdb15093858a6bafe423a23140523d52d5508495a850272db0fe226c02
80942023042c2359d6ab4025ad40f6cb742b7cffd380c4ae9895b39a53e111e6
c1ccccc1
Cl-c1:n:c:c(-[CH2;D2;+0:1]-[C:2](-[c:3])-[C:4](=[O;D1;H0:5])-[#8:6]-[C:7]):c(-Cl):n:1>>[C:7]-[#8:6]-[C:4](=[O;D1;H0:5])-[C:2](-[CH3;D1;+0:1])-[c:3]
null
[]
120
CELSIUS
null
null
The mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(2,5-dimethoxy-phenyl)-propionic acid ethyl ester (0.36 g, 0.94 mmol) (from Example 6a supra) and aniline (2.0 mL) (Aldrich) was heated at 120° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3), and the supernatant was decanted off after each time. T...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide
null
c1cncnc1
null
c1ccccc1
Other
null
120
null
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)ccc1OC>>CCOC(=O)C(C)c1cc(OC)ccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-aa434642a69645fba495e3907de3e968
COC(=O)Cc1ccccc1OC.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC
ClC1=NC=C(C(=N1)Cl)CI.COC(CC1=C(C=CC=C1)OC)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC=C1)OC)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1[O:21][CH3:22].I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1[O:21][CH3:22]
COC(=O)Cc1ccccc1OC.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2-methoxyphenylacetic acid methyl ester (1.8 g, 10.0 mmol) (TCI-US) in tetrahydrofuran...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
COC(=O)Cc1ccccc1OC.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-03f9a95783854b8395a684e5c8db3095
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=C(C=CC=C1)OC)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=C(C=CC=C1)OC)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[cH:28][cH:29][cH:30][cH:31][c:32]2[O:33][CH3:34])[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:24][cH:25][cH:26]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18][c:19]...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC
null
null
null
Aromatic Heterocycle Formation
OtherReaction
17063f9790599d9363915ef3b96d7a5711afaaf38fdeacf6e3cc163a0b39b4e5
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]):[c:6]:[#7;a:7]:1.[NH2;D1;+0:8]-[c;H0;D3;+0:9]1:[c:10]:[cH;D2;+0:11]:[cH;D2;+0:12]:[c:13]:[cH;D2;+0:14]:1>>[C:5]-[c:4]1:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c;H0;D3;+0:9]2:[c:10]:[cH;D2;+0:11]:[c:15]:[c:16]:[c:17]:2):[#7;a:2]:[c;H0;D3;+0:3]:1-[#7:18]-...
null
[]
120
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(2-methoxy-phenyl)-propionic acid methyl ester (0.34 g, 1.0 mmol) (from Example 7a supra) and aniline (2.0 mL) (Aldrich) was heated at 120° C. for 1 hour. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The resid...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
120
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-8312e661429447d69f797ea2a7092eb8
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC>>COc1ccccc1C1Cc2cnc(Nc3ccccc3)nc2N(c2ccccc2)C1=O
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=C(C=CC=C1)OC)=O.S(O)(O)(=O)=O>>COC1=C(C=CC=C1)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CO[C:31]([CH:9]([c:8]1[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][cH:7]1)[CH2:10][c:11]1[cH:12][n:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][cH:21]2)[n:22][c:23]1[NH:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1)=[O:32]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[CH:9]1[CH2:10][c:11]2[cH:12][n:13][c:14]([NH:...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC
COc1ccccc1C1Cc2cnc(Nc3ccccc3)nc2N(c2ccccc2)C1=O
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
110
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(2-dimethoxy-phenyl propionic acid methyl ester (181.8 mg, 0.40 mmol) (from Example 7b supra) was added 5% concentrated sulfuric acid in glacial acetic acid (3 mL) in one portion. The reaction mixture was heated at 110° C. for 3 hours. After cooling, the reaction ...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
110
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccccc1OC>C(C)(=O)O.C(C)(=O)OCC>COc1ccccc1C1Cc2cnc(Nc3ccccc3)nc2N(c2ccccc2)C1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-410bce6426de4dcc9092dfffbf90a523
CO.O=C(O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1>>COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
FC(C=1C=C(C=C(C1)C(F)(F)F)CC(=O)O)(F)F.S(O)(O)(=O)=O.CO>>COC(CC1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O
[CH3:1][OH:2].O[C:3](=[O:4])[CH2:5][c:6]1[cH:7][c:8]([C:9]([F:10])([F:11])[F:12])[cH:13][c:14]([C:15]([F:16])([F:17])[F:18])[cH:19]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:6]1[cH:7][c:8]([C:9]([F:10])([F:11])[F:12])[cH:13][c:14]([C:15]([F:16])([F:17])[F:18])[cH:19]1
CO.O=C(O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
null
null
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[c:4].[C;D1;H3:5]-[OH;D1;+0:6]>>[C;D1;H3:5]-[O;H0;D2;+0:6]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[c:4]
null
[]
null
null
null
null
To a solution of 3,5-bis-trifluoromethylphenylacetic acid (3.0 g, 11.03 mmol) (Aldrich) in methanol (20 mL) was added concentrated sulfuric acid (1.0 mL) and the reaction mixture was heated at reflux overnight. The reaction mixture was concentrated in vacuo. The residue was then diluted with ethyl acetate (100 mL) and ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
null
null
null
CO.O=C(O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1>>COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f440d966f1894a53b2308e1677ea1004
COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1.Clc1ncc(CI)c(Cl)n1>>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
ClC1=NC=C(C(=N1)Cl)CI.COC(CC1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][c:15]1[cH:16][c:17]([C:18]([F:19])([F:20])[F:21])[cH:22][c:23]([C:24]([F:25])([F:26])[F:27])[cH:28]1.I[CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([Cl:11])[n:12][c:13]1[Cl:14])[c:15]1[cH:16][c:17]([C:18]([F:1...
COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1.Clc1ncc(CI)c(Cl)n1
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C;D1;H3:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
10
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 10 minutes, a solution of 3,5-bis-trifluoromethylphenylacetic acid methyl ester (2.20 g, 7.7 mmol) (from Example...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.166667
COC(=O)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1bfc78b0e9c34df2912beabf6aeef46e
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:27]2[cH:28][c:29]([C:30]([F:31])([F:32])[F:33])[cH:34][c:35]([C:21]([F:37])([F:38])[F:39])[cH:40]2)[c:19](Cl)[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
b4dee609a389ff7f843d73232772b98d4a12787647b142169d0155e38d213758
9ea777f6eec6d1dd352e8ec268b374f330238735f05383c104bdeece6906e400
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c;H0;D3;+0:3](-Cl):[c:4](-[C:5]):[c:6]:[#7;a:7]:1.[F;H0;D1;+0:8]-[C;H0;D4;+0:9](-[F;H0;D1;+0:10])(-[F;H0;D1;+0:11])-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16].[NH2;D1;+0:17]-[c:18](:[c:19]):[c:20]>>[C:5]-[c:4]1:[c:6]:[#7;a:7]:[c;H0;D3;+0:1](-[NH;D2;+0:17]-[c:18](:[c:19]):[c:20]):[#7;a:2]...
null
[]
120
CELSIUS
null
null
A mixture of 2-(3,5-bis-trifluoromethyl-phenyl)-3-(2,4-dichloro-pyrimidin-5-yl)-propionic acid methyl ester (0.35 g, 0.78 mmol) (from Example 8b supra) and aniline (2.0 mL) (Aldrich) was heated at 120° C. for 1 hour. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each ...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Aromatic halide.Aromatic halide.Primary amine
Trifluoro group.Secondary amine.Secondary amine
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
120
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fd307c631251414fb63b7d58f5f8cce4
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>>O=C1C(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O.S(O)(O)(=O)=O>>FC(C=1C=C(C=C(C1)C(F)(F)F)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1)(F)F
CO[C:2](=[O:1])[CH:3]([c:4]1[cH:5][c:6]([C:7]([F:8])([F:9])[F:10])[cH:11][c:12]([C:13]([F:14])([F:15])[F:16])[cH:17]1)[CH2:18][c:19]1[cH:20][n:21][c:22]([NH:23][c:24]2[cH:25][cH:26][cH:27][cH:28][cH:29]2)[n:30][c:31]1[NH:32][c:33]1[cH:34][cH:35][cH:36][cH:37][cH:38]1>>[O:1]=[C:2]1[CH:3]([c:4]2[cH:5][c:6]([C:7]([F:8])([...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
O=C1C(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
120
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(3,5-bis-trifluoromethyl-phenyl)-propionic acid methyl ester (0.20 g, 0.36 mmol) (from Example 8c supra) was added 5% concentrated sulfuric acid in glacial acetic acid (3 mL) in one portion. The reaction mixture was heated at 120° C. for 3 hours. The reaction mixt...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
120
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>C(C)(=O)O.C(C)(=O)OCC>O=C1C(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-014700ab78b24173b0516adc76ae8891
CCOC(=O)Cc1ccncc1.Clc1ncc(CI)c(Cl)n1>>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1
ClC1=NC=C(C(=N1)Cl)CI.C(C)OC(CC1=CC=NC=C1)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=NC=C1)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:16]1[cH:17][cH:18][n:19][cH:20][cH:21]1.I[CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15])[c:16]1[cH:17][cH:18][n:19][cH:20][cH:21]1
CCOC(=O)Cc1ccncc1.Clc1ncc(CI)c(Cl)n1
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1cc(CCc2cncnc2)ccn1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14]1:[c:15]:[c:16]:[#7;a:17]:[c:18]:[c:19]:1>>[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14]1:[c:15]:[c:16]:...
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (720 mg, 5.0 mmol) (Aldrich) in dry tetrahydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2.0 mL, 5.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 4-pyridylacetic acid ethyl ester (826 mg, 5.0 mmol) (Lancaster) in tetrahydrofuran (3 mL...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccncc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
CCOC(=O)Cc1ccncc1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c8b46ff25274422d8d420363821a71ce
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccncc1
C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=NC=C1)=O.NC1=CC=CC=C1>>C(C)OC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC=NC=C1)=O
Cl[c:11]1[n:10][cH:9][c:8]([CH2:7][CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:28]2[cH:29][cH:30][n:31][cH:32][cH:33]2)[c:20](Cl)[n:19]1.[NH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([NH:12][c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[n:19][c:2...
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1.Nc1ccccc1
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccncc1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(Nc2ncc(CCc3ccncc3)c(Nc3ccccc3)n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4](-[C:5]):[c;H0;D3;+0:6](-Cl):[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:7]:[c;H0;D3;+0:6]:1-[#7:12]-[c:13]
null
[]
120
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-pyridin-4-yl-propionic acid ethyl ester (0.68 g, 2.0 mmol) (from Example 9a supra) and aniline (3.0 mL) (Aldrich) was heated at 120° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The residue was...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccncc1
null
null
120
null
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccncc1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccncc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-49cc03df8cc74ace9a5489774bcf36d0
CCOC(=O)Cc1cccnc1.Clc1ncc(CI)c(Cl)n1>>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1
ClC1=NC=C(C(=N1)Cl)CI.C(C)OC(CC=1C=NC=CC1)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C=1C=NC=CC1)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:16]1[cH:17][cH:18][cH:19][n:20][cH:21]1.I[CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15])[c:16]1[cH:17][cH:18][cH:19][n:20][cH:21]1
CCOC(=O)Cc1cccnc1.Clc1ncc(CI)c(Cl)n1
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1cncc(CCc2cncnc2)c1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]:[#7;a:17]:[c:18]>>[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]:[#7;a:1...
null
[]
-78
CELSIUS
10
MINUTE
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 10 minutes, a solution of 2-pyridin-3-yl-acetic acid ethyl ester (1.65 g, 10.0 mmol) (Acros) in tetrahydrofuran ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccncc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.166667
CCOC(=O)Cc1cccnc1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-574db29389fe441fb2573534e99b8d0c
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1
C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C=1C=NC=CC1)=O.NC1=CC=CC=C1>>C(C)OC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C=1C=NC=CC1)=O
Cl[c:11]1[n:10][cH:9][c:8]([CH2:7][CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:28]2[cH:29][cH:30][cH:31][n:32][cH:33]2)[c:20](Cl)[n:19]1.[NH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([NH:12][c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[n:19][c:2...
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1.Nc1ccccc1
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(Nc2ncc(CCc3cccnc3)c(Nc3ccccc3)n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4](-[C:5]):[c;H0;D3;+0:6](-Cl):[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:7]:[c;H0;D3;+0:6]:1-[#7:12]-[c:13]
null
[]
120
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-pyridin-3-yl-propionic acid ethyl ester (326 mg, 1.0 mmol) (from Example 10a supra) and aniline (2.0 mL) (Aldrich) was heated at 120° C. for 1 hour. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The residue was...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccncc1
null
null
120
null
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1cccnc1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-710b344f3c0a4faa858fdd396076bad7
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1>>O=C1C(c2cccnc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C(C)OC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C=1C=NC=CC1)=O.S(O)(O)(=O)=O>>C1(=CC=CC=C1)N1C(C(CC2=C1N=C(N=C2)NC2=CC=CC=C2)C=2C=NC=CC2)=O
CCO[C:2](=[O:1])[CH:3]([c:4]1[cH:5][cH:6][cH:7][n:8][cH:9]1)[CH2:10][c:11]1[cH:12][n:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][cH:21]2)[n:22][c:23]1[NH:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1>>[O:1]=[C:2]1[CH:3]([c:4]2[cH:5][cH:6][cH:7][n:8][cH:9]2)[CH2:10][c:11]2[cH:12][n:13][c:14]([NH:15][c:16]3[cH:...
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1
O=C1C(c2cccnc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2cccnc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4]-[c:5]1:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]:[c:10]:1-[NH;D2;+0:11]-[c:12](:[c:13]):[c:14])-[c:15]:[c:16]:[#7;a:17]>>[#7;a:17]:[c:16]:[c:15]-[C:3]1-[C:4]-[c:5]2:[c:6]:[#7;a:7]:[c:8]:[#7;a:9]:[c:10]:2-[N;H0;D3;+0:11](-[c:12](:[c:13]):[c:14])-[C;H0;D3;+0:1]-1=[O;D1;H0:2]
null
[]
120
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-pyridin-3-yl-propionic acid ethyl ester (60 mg, 0.36 mmol) (from Example 10b supra) was added 5% concentrated sulfuric acid in glacial acetic acid (3 mL) in one portion. The reaction mixture was heated at 120° C. for 3 hours. The reaction mixture was then diluted ...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccncc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
120
null
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cccnc1>C(C)(=O)O.C(C)(=O)OCC>O=C1C(c2cccnc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-6595dcbcaa4e4ea4ba99ea2f8bf33099
CCOC(=O)Cc1ccc(OC)c(OC)c1.Clc1ncc(CI)c(Cl)n1>>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1
ClC1=NC=C(C(=N1)Cl)CI.C(C)OC(CC1=CC(=C(C=C1)OC)OC)=O.C(C)(C)NC1CCCCC1.C(CCC)[Li]>>C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=C(C=C1)OC)OC)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][c:16]1[cH:17][cH:18][c:19]([O:20][CH3:21])[c:22]([O:23][CH3:24])[cH:25]1.I[CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([Cl:12])[n:13][c:14]1[Cl:15])[c:16]1[cH:17][cH:18][c:19]([O:20][CH3:21])[...
CCOC(=O)Cc1ccc(OC)c(OC)c1.Clc1ncc(CI)c(Cl)n1
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1
null
null
C(C)(=O)OCC.O1CCCC1
C-C Coupling
OtherReaction
cce1a125a1ff1ac49e6bca841c71f39abbf2c962f7edb2747b8c98f3307cb502
0061a06af9fc64155952582b91b574e4abd8908ca14244f15179c2400b24dd08
c1ccc(CCc2cncnc2)cc1
I-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8].[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH2;D2;+0:13]-[c:14](:[c:15]):[c:16]>>[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[CH;D3;+0:13](-[CH2;D2;+0:1]-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:1-[Cl;D1;H0:8])-[c:14](:[c:15]):[c:16]
null
[]
-78
CELSIUS
30
MINUTE
To a solution of N-isopropylcyclohexylamine (720 mg, 5.0 mmol) (Aldrich) in dry tetrahydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2.0 mL, 5.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 3,4-dimethoxyphenylacetic acid ethyl ester (1.12 g, 5.0 mmol) (Lancaster) in tetrahydrof...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester
Ester
null
null
c1cncnc1.c1ccccc1
HI
C(C)(=O)OCC.O1CCCC1
-78
0.5
CCOC(=O)Cc1ccc(OC)c(OC)c1.Clc1ncc(CI)c(Cl)n1>C(C)(=O)OCC.O1CCCC1>CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7e15299e24944a1ea8f3d98132393c75
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1
C(C)OC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC(=C(C=C1)OC)OC)=O.NC1=CC=CC=C1>>C(C)OC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=C(C=C1)OC)OC)=O
Cl[c:11]1[n:10][cH:9][c:8]([CH2:7][CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:28]2[cH:29][cH:30][c:31]([O:32][CH3:33])[c:34]([O:35][CH3:36])[cH:37]2)[c:20](Cl)[n:19]1.[NH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH2:7][c:8]1[cH:9][n:10][c:11]([NH:12][c:13]2[cH:14][cH:15][c...
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1.Nc1ccccc1
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
41f9322ec5df98feb4edb498f4e5a62751ab580c70737ba501d83b4465521e15
23c6396faba21bf6c4e9de50557b8d044c1caf35494930558fc3d2ba563143ac
c1ccc(CCc2cnc(Nc3ccccc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4](-[C:5]):[c;H0;D3;+0:6](-Cl):[#7;a:7]:1.[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:5]-[c:4]1:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]):[#7;a:7]:[c;H0;D3;+0:6]:1-[#7:12]-[c:13]
null
[]
110
CELSIUS
null
null
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester (440 mg, 1.1 mmol) (from Example 11a supra) and aniline (2.0 mL) (Aldrich) was heated at 110° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Secondary amine.Secondary amine
c1cncnc1
c1cncnc1.c1ccccc1
c1cncnc1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
110
null
CCOC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)c(OC)c1.Nc1ccccc1>>CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f879e793117f44abb15e98d9218b229e
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1OC
C(C)OC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NC1=CC=CC=C1)C1=CC(=C(C=C1)OC)OC)=O.S(O)(O)(=O)=O.C(C)(=O)O>>COC=1C=C(C=CC1OC)C1CC2=C(N=C(N=C2)NC2=CC=CC=C2)N(C1=O)C1=CC=CC=C1
CCO[C:29]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[c:32]([O:33][CH3:34])[cH:31]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[n:20][c:21]1[NH:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1)=[O:30]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([N...
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1
COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1OC
null
null
C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1c1ccccc1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
80
CELSIUS
null
null
To a solution of 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester (470 mg, 0.94 mmol) (from Example 11b supra) in glacial acetic acid (3 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 80° C. overnight. After cooling, the react...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.c1ccccc1
HO-
C(C)(=O)OCC
80
null
CCOC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1ccc(OC)c(OC)c1>C(C)(=O)OCC>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(c3ccccc3)C2=O)cc1OC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0fc233a13f9f4025aae8312c9520c8fc
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1
C(C)(C)N(C(C)C)CC.COC(C(CC=1C(=NC(=NC1)Cl)Cl)C1=CC=C(C=C1)OC)=O.NC1=CC=CC=C1>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)Cl)C1=CC=C(C=C1)OC)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:21]2[cH:22][cH:23][c:24]([O:25][CH3:26])[cH:27][cH:28]2)[c:19]([Cl:20])[n:18]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18...
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1
null
null
C(CCC)O.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(CCc2cnc(Nc3ccccc3)nc2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[c:8]:[c:7](-[NH;D2;+0:6]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]):[c:9]
null
[]
100
CELSIUS
null
null
To a solution of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (341 mg, 1.0 mmol) (from Example 1d supra) in n-butanol (10 mL) was added aniline (200 mg, 2.15 mmol) (Aldrich) followed by N,N-diisopropylethylamine (258 mg, 2.0 mmol) (Aldrich) and the reaction mixture was heated at 100°...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cncnc1.c1ccccc1.c1ccccc1
HCl
C(CCC)O.C(C)(=O)OCC
100
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccc(OC)cc1.Nc1ccccc1>C(CCC)O.C(C)(=O)OCC>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4ec5039ca5784a64aa34542cd4a45e8b
COC(=O)C(Cc1cnc(Cl)nc1Nc1ccccc1)c1ccc(OC)cc1.COc1ccc(N)cn1>>COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1
COC(C(CC=1C(=NC(=NC1)Cl)NC1=CC=CC=C1)C1=CC=C(C=C1)OC)=O.NC=1C=CC(=NC1)OC>>COC(C(CC=1C(=NC(=NC1)NC=1C=NC(=CC1)OC)NC1=CC=CC=C1)C1=CC=C(C=C1)OC)=O
Cl[c:10]1[n:9][cH:8][c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:29]2[cH:30][cH:31][c:32]([O:33][CH3:34])[cH:35][cH:36]2)[c:21]([NH:22][c:23]2[cH:24][cH:25][cH:26][cH:27][cH:28]2)[n:20]1.[NH2:11][c:12]1[cH:13][cH:14][c:15]([O:16][CH3:17])[n:18][cH:19]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]...
COC(=O)C(Cc1cnc(Cl)nc1Nc1ccccc1)c1ccc(OC)cc1.COc1ccc(N)cn1
COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1
null
null
C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(CCc2cnc(Nc3cccnc3)nc2Nc2ccccc2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]:[#7;a:10]:[c:11]>>[c:8]:[c:7](-[NH;D2;+0:6]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]):[c:9]:[#7;a:10]:[c:11]
null
[]
110
CELSIUS
null
null
A mixture of 3-(2-chloro-4-phenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (40 mg, 0.1 mmol) (from Example 12b supra) and 5-amino-2-methoxypyridine (37.2 mg, 0.3 mmol) (Aldrich) was heated at 110° C. for 4 hours. After cooling, the reaction mixture was diluted with ethyl acetate (50 mL) and...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cncnc1.c1ccncc1.c1ccccc1.c1ccccc1
HCl
C(C)(=O)OCC
110
null
COC(=O)C(Cc1cnc(Cl)nc1Nc1ccccc1)c1ccc(OC)cc1.COc1ccc(N)cn1>C(C)(=O)OCC>COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0cc76f6a46d14480921745d16f372339
COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccc(OC)nc4)nc3N(c3ccccc3)C2=O)cc1
COC(C(CC=1C(=NC(=NC1)NC=1C=NC(=CC1)OC)NC1=CC=CC=C1)C1=CC=C(C=C1)OC)=O.S(O)(O)(=O)=O>>COC1=CC=C(C=C1)C1CC2=C(N=C(N=C2)NC=2C=NC(=CC2)OC)N(C1=O)C1=CC=CC=C1
CO[C:31]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:34][cH:33]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][c:17]([O:18][CH3:19])[n:20][cH:21]2)[n:22][c:23]1[NH:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1)=[O:32]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([NH:...
COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1
COc1ccc(C2Cc3cnc(Nc4ccc(OC)nc4)nc3N(c3ccccc3)C2=O)cc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3cccnc3)nc2N1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-[N;H0;D3;+0:12]-1-[c:13](:[c:14]):[c:15]
null
[]
80
CELSIUS
null
null
To a solution of 3-[2-(6-methoxy-pyridin-3-ylamino)-4-phenylamino-pyrimidin-5-yl]-2-(4-methoxy-phenyl)-propionic acid methyl ester (45.0 mg, 0.09 mmol) (from Example 12c supra) in glacial acetic acid (1 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. After heating at 80° C. for 3 hours, the reaction m...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccncc1.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
80
null
COC(=O)C(Cc1cnc(Nc2ccc(OC)nc2)nc1Nc1ccccc1)c1ccc(OC)cc1>C(C)(=O)O.C(C)(=O)OCC>COc1ccc(C2Cc3cnc(Nc4ccc(OC)nc4)nc3N(c3ccccc3)C2=O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-16c01f2bbc1b441a947666da49a93695
CC(C)CN.COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)Cl)C1=CC=C(C=C1)OC)=O.C(C(C)C)N>>C(C(C)C)N1C(C(CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC=C(C=C2)OC)=O
[NH2:22][CH2:23][CH:24]([CH3:25])[CH3:26].CO[C:27]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:30][cH:29]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[n:20][c:21]1Cl)=[O:28]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([NH:13][c:14]4[cH:15][cH...
CC(C)CN.COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1
COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
null
null
null
Acylation
OtherReaction
bb5e32632e312fcbe72f0880005dd462f489b188b3c385ba5cdadc228b7765cb
dc9957f440a17324ed746bff6f1241dbafeab37444abd9e3d9de99ab08a9bd3f
O=C1Nc2nc(Nc3ccccc3)ncc2CC1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9](-[#7:10]):[#7;a:11]:[c;H0;D3;+0:12]:1-Cl.[C:13]-[C:14]-[NH2;D1;+0:15]>>[#7:10]-[c:9]1:[#7;a:8]:[c:7]:[c:6]2:[c;H0;D3;+0:12](:[#7;a:11]:1)-[N;H0;D3;+0:15](-[C:14]-[C:13])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-2
null
[]
null
null
null
null
A mixture of 3-(4-chloro-2-phenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (40 mg, 0.1 mmol) (from Example 12a supra) and isobutylamine (2.0 mL) (Aldrich) was heated at reflux for 3 hours. The reaction mixture was concentrated in vacuo and purified by preparative thin layer chromatography t...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Primary amine
Tertiary amide
c1cncnc1
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1
HCl
null
null
null
CC(C)CN.COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3442685734594738948d4f348ffe24c3
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC(C)C)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NCC(C)C)C1=CC=C(C=C1)OC)=O.S(O)(O)(=O)=O>>C(C(C)C)N1C(C(CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC=C(C=C2)OC)=O
CO[C:27]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:30][cH:29]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[n:20][c:21]1[NH:22][CH2:23][CH:24]([CH3:25])[CH3:26])=[O:28]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([NH:13][c:14]4[cH:15][cH:16]...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC(C)C)c1ccc(OC)cc1
COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1Nc2nc(Nc3ccccc3)ncc2CC1c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[C:13]-[C:14]>>[C:14]-[C:13]-[N;H0;D3;+0:12]1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-1
null
[]
85
CELSIUS
null
null
To the solution of 3-(2-phenylamino-4-isobutylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (17.1 mg, 0.04 mmol) in glacial acetic acid (1 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 85° C. overnight. After cooling, the reaction mixture w...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1
HO-
C(C)(=O)O.C(C)(=O)OCC
85
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC(C)C)c1ccc(OC)cc1>C(C)(=O)O.C(C)(=O)OCC>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC(C)C)C2=O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-38451a5aa7434de7b8a658e3baae8e64
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1.NCC1CC1>>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)Cl)C1=CC=C(C=C1)OC)=O.C1(CC1)CN>>COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NCC1CC1)C1=CC=C(C=C1)OC)=O
Cl[c:19]1[c:7]([CH2:6][CH:5]([C:3]([O:2][CH3:1])=[O:4])[c:25]2[cH:26][cH:27][c:28]([O:29][CH3:30])[cH:31][cH:32]2)[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18]1.[NH2:20][CH2:21][CH:22]1[CH2:23][CH2:24]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][c...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1.NCC1CC1
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1
null
null
C(C)(=O)OCC
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(CCc2cnc(Nc3ccccc3)nc2NCC2CC2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[#7:4]):[#7;a:5]:[c:6]:[c:7]:1-[C:8].[C:9]-[C:10]-[NH2;D1;+0:11]>>[#7:4]-[c:3]1:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:11]-[C:10]-[C:9]):[c:7](-[C:8]):[c:6]:[#7;a:5]:1
null
[]
null
null
24
HOUR
A mixture of 3-(4-chloro-2-phenylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (45 mg, 0.11 mmol) (from Example 12a supra) and cyclopropylmethylamine (1.0 mL) (Lancaster) was stirred at room temperature for 24 hours. The reaction mixture was then diluted with ethyl acetate (50 mL) and successiv...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cncnc1.c1ccccc1.C1CC1.c1ccccc1
HCl
C(C)(=O)OCC
null
24
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Cl)c1ccc(OC)cc1.NCC1CC1>C(C)(=O)OCC>COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4c05c88a2a714ca08093234ae20c2763
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1>>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC3CC3)C2=O)cc1
COC(C(CC=1C(=NC(=NC1)NC1=CC=CC=C1)NCC1CC1)C1=CC=C(C=C1)OC)=O.S(O)(O)(=O)=O>>C1(CC1)CN1C(C(CC2=C1N=C(N=C2)NC2=CC=CC=C2)C2=CC=C(C=C2)OC)=O
CO[C:27]([CH:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:30][cH:29]1)[CH2:8][c:9]1[cH:10][n:11][c:12]([NH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][cH:19]2)[n:20][c:21]1[NH:22][CH2:23][CH:24]1[CH2:25][CH2:26]1)=[O:28]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH:7]2[CH2:8][c:9]3[cH:10][n:11][c:12]([NH:13][c:14]4[cH:15][cH:16]...
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1
COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC3CC3)C2=O)cc1
null
null
C(C)(=O)O.C(C)(=O)OCC
Miscellaneous
OtherReaction
4c156791040233b925f911d2344eae0f4fe404d66aa7be29ecbd3d34ec58b9ee
9fb754180ed1affe0187ff01b0205aba264dc674a9ca4b55d9d8c90d1514940e
O=C1C(c2ccccc2)Cc2cnc(Nc3ccccc3)nc2N1CC1CC1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]1:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH;D2;+0:12]-[C:13]-[C:14]>>[C:14]-[C:13]-[N;H0;D3;+0:12]1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[c:6]2:[c:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:2-1
null
[]
85
CELSIUS
null
null
To a solution of crude 3-(2-phenylamino-4-cyclopropylmethylamino-pyrimidin-5-yl)-2-(4-methoxy-phenyl)-propionic acid methyl ester (51.3 mg) (from Example 14a supra) in glacial acetic acid (1 mL) was added concentrated sulfuric acid (0.1 mL) in one portion. The reaction mixture was heated at 85° C. for 3 hours. The reac...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide
null
c1ncc2c(n1)[NH]CCC2
c1ccccc1.c1ncc2c(n1)[NH]CCC2.c1ccccc1.C1CC1
HO-
C(C)(=O)O.C(C)(=O)OCC
85
null
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1NCC1CC1)c1ccc(OC)cc1>C(C)(=O)O.C(C)(=O)OCC>COc1ccc(C2Cc3cnc(Nc4ccccc4)nc3N(CC3CC3)C2=O)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-6250fc794fad4744874872c3b677d7df
CCOC(=O)CC(=O)C(F)(F)F.Oc1ccc(Cc2ccccc2)cc1>>O=c1cc(C(F)(F)F)c2cc(Cc3ccccc3)ccc2o1
C(C1=CC=CC=C1)C1=CC=C(C=C1)O.C(F)(F)(F)C(=O)CC(=O)OCC.CS(=O)(=O)O>>C(C1=CC=CC=C1)C=1C=C2C(=CC(OC2=CC1)=O)C(F)(F)F
CCO[C:2](=[O:1])[CH2:3][C:4](=O)[C:5]([F:6])([F:7])[F:8].[cH:9]1[cH:10][c:11]([CH2:12][c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[cH:19][cH:20][c:21]1[OH:22]>>[O:1]=[c:2]1[cH:3][c:4]([C:5]([F:6])([F:7])[F:8])[c:9]2[cH:10][c:11]([CH2:12][c:13]3[cH:14][cH:15][cH:16][cH:17][cH:18]3)[cH:19][cH:20][c:21]2[o:22]1
CCOC(=O)CC(=O)C(F)(F)F.Oc1ccc(Cc2ccccc2)cc1
O=c1cc(C(F)(F)F)c2cc(Cc3ccccc3)ccc2o1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
c2797b9482351455dfd80600e9316aa63917d1f2fdbd6de4297ad8f5b4bfbe49
89a9e45776dbe9070f40025f4f55f2a7b9907ff5b9cebad1727718d85938e303
O=c1ccc2cc(Cc3ccccc3)ccc2o1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](=O)-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8].[OH;D1;+0:9]-[c:10](:[c:11]):[cH;D2;+0:12]:[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](=[O;D1;H0:2]):[o;H0;D2;+0:9]:[c:10](:[c:11]):[c;H0;D3;+0:1...
44.3
[{"value": 44.0, "product": "C(C1=CC=CC=C1)C=1C=C2C(=CC(OC2=CC1)=O)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.3, "product": "C(C1=CC=CC=C1)C=1C=C2C(=CC(OC2=CC1)=O)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
null
null
A stirred suspension of 4-benzylphenol (4.67 g, 25.4 mmol), CF3COCH2CO2Et (7.00 g, 38.0 mmol), & MeSO3H (8.5 mL, 130.9 mmol) was heated at 65° C. for 9 h. On cooling, the mixture was partitioned between Et2O (200 mL) & H2O (50 mL), then the aqueous phase was basicified with 2 M NaOH. The organic layer was separated & w...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Aromatic alcohol
null
c1ccccc1
c1ccc2occcc2c1
c1ccc2occcc2c1.c1ccccc1
HO-
null
65
null
CCOC(=O)CC(=O)C(F)(F)F.Oc1ccc(Cc2ccccc2)cc1>>O=c1cc(C(F)(F)F)c2cc(Cc3ccccc3)ccc2o1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9d9accae0f0f4ed7971d30ee908f5890
CC(C)N.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>>CC(C)NS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
CCOC(=O)C.O=C1NC2=CC=C(C=C2C(=C1)C(F)(F)F)CC1=CC=C(C=C1)S(=O)(=O)Cl.C(C)(C)N>>C(C)(C)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F
[CH3:1][CH:2]([CH3:3])[NH2:4].Cl[S:5](=[O:6])(=[O:7])[c:8]1[cH:9][cH:10][c:11]([CH2:12][c:13]2[cH:14][cH:15][c:16]3[nH:17][c:18](=[O:19])[cH:20][c:21]([C:22]([F:23])([F:24])[F:25])[c:26]3[cH:27]2)[cH:28][cH:29]1>>[CH3:1][CH:2]([CH3:3])[NH:4][S:5](=[O:6])(=[O:7])[c:8]1[cH:9][cH:10][c:11]([CH2:12][c:13]2[cH:14][cH:15][c:...
CC(C)N.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1
CC(C)NS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
null
null
C(Cl)Cl
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=c1ccc2cc(Cc3ccccc3)ccc2[nH]1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C;D1;H3:7]-[C:8](-[C;D1;H3:9])-[NH2;D1;+0:10]>>[C;D1;H3:7]-[C:8](-[C;D1;H3:9])-[NH;D2;+0:10]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
45
[{"value": 45.0, "product": "C(C)(C)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.9, "product": "C(C)(C)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
20
CELSIUS
10
MINUTE
A stirred solution of 4-(2-oxo4-trifluoromethyl-1,2-dihydroquinolin-6-ylmethyl)-benzenesulfonyl chloride (Preparation 1, 17 mg, 42 μmol) in anhydrous CH2Cl2 (0.5 mL) was treated dropwise with an excess of i-PrNH2 (145 μL, 1680 μmol). After stirring at 20° C. for 10 min, the reaction mixture was submitted to column chro...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccc2ncccc2c1
HCl
C(Cl)Cl
20
0.166667
CC(C)N.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>C(Cl)Cl>CC(C)NS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c0c4244a11c84b8bb0979a414d3e20be
CCCCN.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>>CCCCNS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
O=C1NC2=CC=C(C=C2C(=C1)C(F)(F)F)CC1=CC=C(C=C1)S(=O)(=O)Cl.C(CCC)N>>C(CCC)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F
[CH3:1][CH2:2][CH2:3][CH2:4][NH2:5].Cl[S:6](=[O:7])(=[O:8])[c:9]1[cH:10][cH:11][c:12]([CH2:13][c:14]2[cH:15][cH:16][c:17]3[nH:18][c:19](=[O:20])[cH:21][c:22]([C:23]([F:24])([F:25])[F:26])[c:27]3[cH:28]2)[cH:29][cH:30]1>>[CH3:1][CH2:2][CH2:3][CH2:4][NH:5][S:6](=[O:7])(=[O:8])[c:9]1[cH:10][cH:11][c:12]([CH2:13][c:14]2[cH...
CCCCN.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1
CCCCNS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=c1ccc2cc(Cc3ccccc3)ccc2[nH]1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C:7]-[C:8]-[NH2;D1;+0:9]>>[C:7]-[C:8]-[NH;D2;+0:9]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
91.2
[{"value": 84.0, "product": "C(CCC)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.2, "product": "C(CCC)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-(2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-6-ylmethyl)benzenesulfonyl chloride (Preparation 1, 26 mg, 65 μmol) was reacted with an excess of n-BuNH2 (190 mg, 2600 μmol) by the same procedure used for Example 1. After reaction, the solvents were evaporated off under reduced pressure & the residue partitioned between...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccc2ncccc2c1
HCl
null
null
null
CCCCN.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>>CCCCNS(=O)(=O)c1ccc(Cc2ccc3[nH]c(=O)cc(C(F)(F)F)c3c2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cbdf752bc7c248abbc942b21d3cffc35
NCc1ccccc1.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>>O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)NCc4ccccc4)cc3)ccc2[nH]1
O=C1NC2=CC=C(C=C2C(=C1)C(F)(F)F)CC1=CC=C(C=C1)S(=O)(=O)Cl.C(C1=CC=CC=C1)N>>C(C1=CC=CC=C1)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F
[NH2:20][CH2:21][c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1.Cl[S:17]([c:16]1[cH:15][cH:14][c:13]([CH2:12][c:11]2[cH:10][c:9]3[c:4]([C:5]([F:6])([F:7])[F:8])[cH:3][c:2](=[O:1])[nH:33][c:32]3[cH:31][cH:30]2)[cH:29][cH:28]1)(=[O:18])=[O:19]>>[O:1]=[c:2]1[cH:3][c:4]([C:5]([F:6])([F:7])[F:8])[c:9]2[cH:10][c:11]([CH2:12][c:1...
NCc1ccccc1.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1
O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)NCc4ccccc4)cc3)ccc2[nH]1
null
null
null
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=c1ccc2cc(Cc3ccc(S(=O)(=O)NCc4ccccc4)cc3)ccc2[nH]1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[C:8]-[c:9]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[C:8]-[c:9])-[c:4](:[c:5]):[c:6]
61.9
[{"value": 61.0, "product": "C(C1=CC=CC=C1)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.9, "product": "C(C1=CC=CC=C1)NS(=O)(=O)C1=CC=C(C=C1)CC=1C=C2C(=CC(NC2=CC1)=O)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Reaction of 4-(2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-6-ylmethyl)benzene-sulfonyl chloride (Preparation 1, 26 mg, 65 μmol) with an excess of BnNH2 (280 mg, 2600 μmol), by the method described for Example 1, generated the title compound (19 mg, 61%): δH ((CD3)2SO)=3.95 (d, 2H), 4.15 (s, 2H), 7.00 (s, 1H), 7.15–7.25...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccc2ncccc2c1.c1ccccc1.c1ccccc1
HCl
null
null
null
NCc1ccccc1.O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)Cl)cc3)ccc2[nH]1>>O=c1cc(C(F)(F)F)c2cc(Cc3ccc(S(=O)(=O)NCc4ccccc4)cc3)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1b0ea0d9e5564b47bba4617ca3b34571
Oc1ccccc1>>CCCC(=O)O.CCCCCC
C(=O)([O-])[O-].[K+].[K+].C1(=CC=CC=C1)O>>CCCCCC.C(C)CC(=O)O
O[c:1]1[cH:7][cH:8][cH:9][cH:10][cH:11]1>>[CH3:1][CH2:2][CH2:3][C:4](=[O:5])[OH:6].[CH3:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Oc1ccccc1
CCCC(=O)O.CCCCCC
null
null
C(C)#N
Miscellaneous
OtherReaction
fa618f5452cf8d39f77ddf913f06d82fa923daf39ff606905a5341ace0bd65f7
45b5980231007c8958a67317ea24d97c426ebaa02282f06c70b75eb4ce8f769b
null
O-[c;H0;D3;+0:1]1:[cH;D2;+0:2]:[cH;D2;+0:3]:[cH;D2;+0:4]:[cH;D2;+0:5]:[cH;D2;+0:6]:1>>[C;D1;H3:7]-[CH2;D2;+0:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[CH2;D2;+0:5]-[CH3;D1;+0:6].[C:8]-[C:9]-[CH3;D1;+0:1]
null
[]
null
null
1
HOUR
O-methyl(ethyl) O-aryl chlorothiophosphate, which was obtained by reacting O-methyl(ethyl) dichlorothiophosphate with phenol, was reacted with aminocarboxylic acid to give a hapten for immunoassay of phosphorothioate pesticides: to 46 mmol of O-methyl(ethyl) dichlorothiophosphate (10) dissolved in 30 mL of acetonitrile...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Carboxylic acid
c1ccccc1
null
null
null
C(C)#N
null
1
Oc1ccccc1>C(C)#N>CCCC(=O)O.CCCCCC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9ddc7e8714f848aa8be681a6021447c6
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
C1(=CC=CC=C1)C.CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NN=NN5C(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8)C(=O)OC(C)OC(=O)OC9CCCCC9.C(=O)O>>CCOC1=NC=2C=CC=C(C2N1CC=3C=CC(=CC3)C=4C=CC=CC4C5=NNN=N5)C(=O)OC(C)OC(=O)OC6CCCCC6
c1ccc(C(c2ccccc2)(c2ccccc2)[n:43]2[c:39](-[c:38]3[c:33](-[c:32]4[cH:31][cH:30][c:29]([CH2:28][n:27]5[c:4]([O:3][CH2:2][CH3:1])[n:5][c:6]6[cH:7][cH:8][cH:9][c:10]([C:11](=[O:12])[O:13][CH:14]([CH3:15])[O:16][C:17](=[O:18])[O:19][CH:20]7[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]7)[c:26]65)[cH:45][cH:44]4)[cH:34][cH:35][cH:...
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
null
null
CO
Deprotection
OtherReaction
bee75b2c80e33b32bc1cd2f4da11999883aae9c37547c33804aee63f103057c6
30a26bc929988d0041b9998cdccd1d65eb125114a78065ed35d40f50c965c0a7
O=C(OCOC(=O)c1cccc2ncn(Cc3ccc(-c4ccccc4-c4nn[nH]n4)cc3)c12)OC1CCCCC1
[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[n;H0;D2;+0:5]:[n;H0;D3;+0:6]:1-C(-c1:c:c:c:c:c:1)(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[nH;D2;+0:5]:[n;H0;D2;+0:6]:1
null
[]
null
null
null
null
Typically, the deprotection step comprises heating to reflux trityl candesartan cilexetil in methanol. Optionally, the deprotection solvent mixture further comprises an organic solvent, such as toluene, and/or an acid, such as formic acid. The cilexetil trityl candesartan is heated to reflux until a clear solution is o...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccccc1.c1ccccc1.c1ccccc1.c1nnn[nH]1
c1nnn[nH]1
c1nc2ccccc2[nH]1.C1CCCCC1.c1ccccc1.c1ccccc1.c1nnn[nH]1
Other
CO
null
null
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>CO>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cf2755c8bda948af8d1a138c3269dbe4
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NN=NN5C(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8)C(=O)OC(C)OC(=O)OC9CCCCC9.C1(=CC=CC=C1)C.CO>>CCOC1=NC=2C=CC=C(C2N1CC=3C=CC(=CC3)C=4C=CC=CC4C5=NNN=N5)C(=O)OC(C)OC(=O)OC6CCCCC6
c1ccc(C(c2ccccc2)(c2ccccc2)[n:43]2[c:39](-[c:38]3[c:33](-[c:32]4[cH:31][cH:30][c:29]([CH2:28][n:27]5[c:4]([O:3][CH2:2][CH3:1])[n:5][c:6]6[cH:7][cH:8][cH:9][c:10]([C:11](=[O:12])[O:13][CH:14]([CH3:15])[O:16][C:17](=[O:18])[O:19][CH:20]7[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]7)[c:26]65)[cH:45][cH:44]4)[cH:34][cH:35][cH:...
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
null
null
O
Deprotection
OtherReaction
bee75b2c80e33b32bc1cd2f4da11999883aae9c37547c33804aee63f103057c6
30a26bc929988d0041b9998cdccd1d65eb125114a78065ed35d40f50c965c0a7
O=C(OCOC(=O)c1cccc2ncn(Cc3ccc(-c4ccccc4-c4nn[nH]n4)cc3)c12)OC1CCCCC1
[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[n;H0;D2;+0:5]:[n;H0;D3;+0:6]:1-C(-c1:c:c:c:c:c:1)(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[nH;D2;+0:5]:[n;H0;D2;+0:6]:1
null
[]
null
null
null
null
A mixture of trityl candesartan cilexetil (20 g, 23.45 mmol), toluene (60 ml), methanol (60 ml), and water (1 ml) was gently refluxed for about 12 h. The reaction was monitored by HPLC. The solution volume was reduced by evaporation under reduced pressure (30 mbar) at a temperature of about 55° C. 60° C. to obtain visc...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccccc1.c1ccccc1.c1ccccc1.c1nnn[nH]1
c1nnn[nH]1
c1nc2ccccc2[nH]1.C1CCCCC1.c1ccccc1.c1ccccc1.c1nnn[nH]1
Other
O
null
null
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>O>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-81a6ecf14d144689918ebb497d08a2d5
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NN=NN5C(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8)C(=O)OC(C)OC(=O)OC9CCCCC9.C1(=CC=CC=C1)C.CO>>CCOC1=NC=2C=CC=C(C2N1CC=3C=CC(=CC3)C=4C=CC=CC4C5=NNN=N5)C(=O)OC(C)OC(=O)OC6CCCCC6
c1ccc(C(c2ccccc2)(c2ccccc2)[n:43]2[c:39](-[c:38]3[c:33](-[c:32]4[cH:31][cH:30][c:29]([CH2:28][n:27]5[c:4]([O:3][CH2:2][CH3:1])[n:5][c:6]6[cH:7][cH:8][cH:9][c:10]([C:11](=[O:12])[O:13][CH:14]([CH3:15])[O:16][C:17](=[O:18])[O:19][CH:20]7[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]7)[c:26]65)[cH:45][cH:44]4)[cH:34][cH:35][cH:...
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
null
null
O
Deprotection
OtherReaction
bee75b2c80e33b32bc1cd2f4da11999883aae9c37547c33804aee63f103057c6
30a26bc929988d0041b9998cdccd1d65eb125114a78065ed35d40f50c965c0a7
O=C(OCOC(=O)c1cccc2ncn(Cc3ccc(-c4ccccc4-c4nn[nH]n4)cc3)c12)OC1CCCCC1
[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[n;H0;D2;+0:5]:[n;H0;D3;+0:6]:1-C(-c1:c:c:c:c:c:1)(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[nH;D2;+0:5]:[n;H0;D2;+0:6]:1
null
[]
null
null
null
null
A mixture of trityl candesartan cilexetil (20 g, 23.45 mmol), toluene (60 ml), methanol (120 ml), and water (1 ml) was gently refluxed for about 5 h. The reaction progress was monitored by HPLC. The solution volume was reduced by evaporation under reduced pressure (30 mbar) at a temperature of about 55° C. to 60° C. to...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccccc1.c1ccccc1.c1ccccc1.c1nnn[nH]1
c1nnn[nH]1
c1nc2ccccc2[nH]1.C1CCCCC1.c1ccccc1.c1ccccc1.c1nnn[nH]1
Other
O
null
null
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>O>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-058db254e82c45b7899abb07338a96ad
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NN=NN5C(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8)C(=O)OC(C)OC(=O)OC9CCCCC9.CO>>CCOC1=NC=2C=CC=C(C2N1CC=3C=CC(=CC3)C=4C=CC=CC4C5=NNN=N5)C(=O)OC(C)OC(=O)OC6CCCCC6
c1ccc(C(c2ccccc2)(c2ccccc2)[n:43]2[c:39](-[c:38]3[c:33](-[c:32]4[cH:31][cH:30][c:29]([CH2:28][n:27]5[c:4]([O:3][CH2:2][CH3:1])[n:5][c:6]6[cH:7][cH:8][cH:9][c:10]([C:11](=[O:12])[O:13][CH:14]([CH3:15])[O:16][C:17](=[O:18])[O:19][CH:20]7[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]7)[c:26]65)[cH:45][cH:44]4)[cH:34][cH:35][cH:...
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
null
null
O
Deprotection
OtherReaction
bee75b2c80e33b32bc1cd2f4da11999883aae9c37547c33804aee63f103057c6
30a26bc929988d0041b9998cdccd1d65eb125114a78065ed35d40f50c965c0a7
O=C(OCOC(=O)c1cccc2ncn(Cc3ccc(-c4ccccc4-c4nn[nH]n4)cc3)c12)OC1CCCCC1
[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[n;H0;D2;+0:5]:[n;H0;D3;+0:6]:1-C(-c1:c:c:c:c:c:1)(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[c:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[nH;D2;+0:5]:[n;H0;D2;+0:6]:1
null
[]
null
null
null
null
A mixture of trityl candesartan cilexetil (20 g, 23.45 mmol), methanol (200 ml), and water (1 ml) was gently refluxed for about 16–17 h. The reaction progress was monitored by HPLC. The solution volume was reduced by evaporation under reduced pressure (30 mbar) at a temperature of 55° C. to 60° C. to obtain viscous oil...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccccc1.c1ccccc1.c1ccccc1.c1nnn[nH]1
c1nnn[nH]1
c1nc2ccccc2[nH]1.C1CCCCC1.c1ccccc1.c1ccccc1.c1nnn[nH]1
Other
O
null
null
CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1>O>CCOc1nc2cccc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c3f0ffdbe3a147e5b8c4869da58c2e70
O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(Cl)c(Cl)c1>>O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1c1cc(Cl)c(Cl)cc1[N+](=O)[O-]
C(=O)(OCC1=CC=CC=C1)N1C[C@@H](NCC1)C(=O)O.ClC1=C(C(=CC(=C1)[N+](=O)[O-])F)Cl.O.CN(C=O)C>>C(=O)(OCC1=CC=CC=C1)N1C[C@@H](N(CC1)C1=C(C=C(C(=C1)Cl)Cl)[N+](=O)[O-])C(=O)O
[O:1]=[C:2]([OH:3])[C@H:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17][CH2:18][NH:19]1.F[c:24]1[c:22]([Cl:23])[c:21]([Cl:25])[cH:20][c:27]([N+:28](=[O:29])[O-:30])[cH:26]1>>[O:1]=[C:2]([OH:3])[C@H:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:1...
O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(Cl)c(Cl)c1
O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1c1cc(Cl)c(Cl)cc1[N+](=O)[O-]
null
null
C(C)N(CC)CC
Functional Group Interconversion
OtherReaction
dd7353043b9be5eeb7c17f31c462d2a9bc114e2e9d3d13fac984a45e43d4b2cd
f53962194c2216e08e7685a4ca49aa3deb09685291e557c1a0b20a4dc85a77b5
O=C(OCc1ccccc1)N1CCN(c2ccccc2)CC1
F-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[#7;+:4]):[cH;D2;+0:5]:[c;H0;D3;+0:6](-[Cl;H0;D1;+0:7]):[c:8]:1-[Cl;D1;H0:9].[O;D1;H0:10]=[C:11](-[O;D1;H1:12])-[C:13]1-[C:14]-[#7:15]-[C:16]-[C:17]-[NH;D2;+0:18]-1>>[#7;+:4]-[c:3]1:[c:2]:[c;H0;D3;+0:1](-[Cl;H0;D1;+0:7]):[c:8](-[Cl;D1;H0:9]):[cH;D2;+0:6]:[c;H0;D3;+0:5]:1-[N;H0;D3;+0:18]1-...
94.2
[{"value": 94.2, "product": "C(=O)(OCC1=CC=CC=C1)N1C[C@@H](N(CC1)C1=C(C=C(C(=C1)Cl)Cl)[N+](=O)[O-])C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.2, "product": "C(=O)(OCC1=CC=CC=C1)N1C[C@@H](N(CC1)C1=C(C=C(C(=C1)Cl)Cl)[N+](=O)[O-])C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false...
50
CELSIUS
null
null
To a slurry containing 5.0 g of (R)-4-carbobenzyloxypiperazine-2-carboxylic acid, 4.2 g of 1,2-dichloro-fluoro-5-nitrobenzene, 85 mL of water and 170 mL of dimethylformamide is added slowly 5.3 mL of triethylamine. The solution is heated to 50° C. for 5 hours, then at ambient temperature overnight. The dark orange solu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Secondary amine
Aromatic halide.Tertiary amine
C1CNCC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HF
C(C)N(CC)CC
50
null
O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(Cl)c(Cl)c1>C(C)N(CC)CC>O=C(O)[C@H]1CN(C(=O)OCc2ccccc2)CCN1c1cc(Cl)c(Cl)cc1[N+](=O)[O-]
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5afd81cea1474aa1b6e2b9885c61c1a1
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1ccc(Cl)c(Cl)c1Cl>>O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl
ClC1=C(C=CC(=C1Cl)Cl)[N+](=O)[O-].C(=O)(OCC1=CC=CC=C1)N1CC(NCC1)C(=O)O>>C(=O)(OCC1=CC=CC=C1)N1CC(N(CC1)C1=C(C=CC(=C1Cl)Cl)[N+](=O)[O-])C(=O)O
[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17][CH2:18][NH:19]1.Cl[c:20]1[c:21]([N+:22](=[O:23])[O-:24])[cH:25][cH:26][c:27]([Cl:28])[c:29]1[Cl:30]>>[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][...
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1ccc(Cl)c(Cl)c1Cl
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl
null
null
null
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
75de53007ec0cb91435746fdefbf3b121f745fc71ddebd19c6e45a5212b3f56a
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=C(OCc1ccccc1)N1CCN(c2ccccc2)CC1
Cl-[c;H0;D3;+0:1](:[c:2](-[#7;+:3]):[c:4]):[c:5](-[Cl;D1;H0:6]):[c:7].[O;D1;H0:8]=[C:9](-[O;D1;H1:10])-[C:11]1-[C:12]-[#7:13]-[C:14]-[C:15]-[NH;D2;+0:16]-1>>[#7;+:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[N;H0;D3;+0:16]1-[C:15]-[C:14]-[#7:13]-[C:12]-[C:11]-1-[C:9](=[O;D1;H0:8])-[O;D1;H1:10]):[c:5](-[Cl;D1;H0:6]):[c:7]
43.6
[{"value": 43.6, "product": "C(=O)(OCC1=CC=CC=C1)N1CC(N(CC1)C1=C(C=CC(=C1Cl)Cl)[N+](=O)[O-])C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the same procedure described for Example 7 A, from 0.86 g of 2,3,4-trichloro-nitro-benzene and 1.0 g of 4-carbobenzyloxypiperazine-2-carboxylic acid, there was obtained 0.75 g of the desired product as a brown oil. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HCl
null
null
null
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1ccc(Cl)c(Cl)c1Cl>>O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e737455c44f54ee7a737fd439bc448cd
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl>>O=C1Nc2ccc(Cl)c(Cl)c2N2CCN(C(=O)OCc3ccccc3)CC12
C(=O)(OCC1=CC=CC=C1)N1CC(N(CC1)C1=C(C=CC(=C1Cl)Cl)[N+](=O)[O-])C(=O)O>>C(=O)(OCC1=CC=CC=C1)N1CC2N(C3=C(C(=CC=C3NC2=O)Cl)Cl)CC1
O=[N+:3]([O-])[c:4]1[cH:5][cH:6][c:7]([Cl:8])[c:9]([Cl:10])[c:11]1[N:12]1[CH2:13][CH2:14][N:15]([C:16](=[O:17])[O:18][CH2:19][c:20]2[cH:21][cH:22][cH:23][cH:24][cH:25]2)[CH2:26][CH:27]1[C:2](O)=[O:1]>>[O:1]=[C:2]1[NH:3][c:4]2[cH:5][cH:6][c:7]([Cl:8])[c:9]([Cl:10])[c:11]2[N:12]2[CH2:13][CH2:14][N:15]([C:16](=[O:17])[O:1...
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl
O=C1Nc2ccc(Cl)c(Cl)c2N2CCN(C(=O)OCc3ccccc3)CC12
null
[Fe]
null
Functional Group Interconversion
OtherReaction
7913e2370debe9ca401402b204be4fcb57433cf616af0012527eda5fc5434821
98c112fcc8dd821704dc378798368c2081a2acc574356674c70af3e59954ee0d
O=C1Nc2ccccc2N2CCN(C(=O)OCc3ccccc3)CC12
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4]-[#7:5])-[#7:6](-[c:7]:[c:8](-[N+;H0;D3:9](=O)-[O-]):[c:10])-[C:11]>>[#7:5]-[C:4]-[C:3]1-[#7:6](-[C:11])-[c:7]:[c:8](:[c:10])-[NH;D2;+0:9]-[C;H0;D3;+0:1]-1=[O;D1;H0:2]
50.7
[{"value": 49.0, "product": "C(=O)(OCC1=CC=CC=C1)N1CC2N(C3=C(C(=CC=C3NC2=O)Cl)Cl)CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 50.7, "product": "C(=O)(OCC1=CC=CC=C1)N1CC2N(C3=C(C(=CC=C3NC2=O)Cl)Cl)CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
By the same procedure described for Example 7B, from 0.75 g of 4-carbobenzyloxy-1-(5,6-dichloro-2-nitrophenyl)piperazine-2-carboxylic acid and 0.28 g of iron powder, there was obtained 0.34 g (49%) of the desired product as a brown solid. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Nitro group
Secondary amide
null
c1ccc2c(c1)NCC1C[NH]CCN21
c1ccc2c(c1)NCC1C[NH]CCN21.c1ccccc1
Other
[Fe]
null
null
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1c([N+](=O)[O-])ccc(Cl)c1Cl>[Fe]>O=C1Nc2ccc(Cl)c(Cl)c2N2CCN(C(=O)OCc3ccccc3)CC12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0b831c4cee1d41bab17511239d6c8b09
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(F)cc1F>>O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1cc(F)c(F)cc1[N+](=O)[O-]
C(=O)(OCC1=CC=CC=C1)N1CC(NCC1)C(=O)O.FC1=C(C=C(C(=C1)[N+](=O)[O-])F)F>>C(=O)(OCC1=CC=CC=C1)N1CC(N(CC1)C1=C(C=C(C(=C1)F)F)[N+](=O)[O-])C(=O)O
[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17][CH2:18][NH:19]1.F[c:20]1[cH:21][c:22]([F:23])[c:24]([F:25])[cH:26][c:27]1[N+:28](=[O:29])[O-:30]>>[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][N:6]([C:7](=[O:8])[O:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:...
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(F)cc1F
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1cc(F)c(F)cc1[N+](=O)[O-]
null
null
null
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
75de53007ec0cb91435746fdefbf3b121f745fc71ddebd19c6e45a5212b3f56a
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=C(OCc1ccccc1)N1CCN(c2ccccc2)CC1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[O;D1;H0:7]=[C:8](-[O;D1;H1:9])-[C:10]1-[C:11]-[#7:12]-[C:13]-[C:14]-[NH;D2;+0:15]-1>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[N;H0;D3;+0:15]1-[C:14]-[C:13]-[#7:12]-[C:11]-[C:10]-1-[C:8](=[O;D1;H0:7])-[O;D1;H1:9]):[c:2]:[c:3]
16.7
[{"value": 16.7, "product": "C(=O)(OCC1=CC=CC=C1)N1CC(N(CC1)C1=C(C=C(C(=C1)F)F)[N+](=O)[O-])C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
By the same procedure described for example 2 method 2B, from 1.5 g of racemic 4-carbobenzyloxypiperazine-2-carboxylic acid and 1,2,4-trifluoro-5-nitro-benzene, there was obtained 0.4 g (16.7%) of title compound as an orange-red residue. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HF
null
null
null
O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1.O=[N+]([O-])c1cc(F)c(F)cc1F>>O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1cc(F)c(F)cc1[N+](=O)[O-]
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c6bf3ab9737a4f4b86487ecc57403964
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1>>Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
Cl.CN(C)CC1CCC=2N(C3=CC=CC=C3C2C1=O)C.CC=1NC=CN1.O>>CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O
CN(C)[CH2:7][CH:8]1[CH2:9][CH2:10][c:11]2[c:12]([c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3[n:19]2[CH3:20])[C:21]1=[O:22].[CH3:1][c:2]1[n:3][cH:4][cH:5][nH:6]1>>[CH3:1][c:2]1[n:3][cH:4][cH:5][n:6]1[CH2:7][CH:8]1[CH2:9][CH2:10][c:11]2[c:12]([c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3[n:19]2[CH3:20])[C:21]1=[O:22]
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1
Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
baea70c3ed4e23fb3981a811d0c5d5797285f34961f974af088dbe9c4c60dd14
7c33147a6170e63e1fbe1110c4ce069481be57a96b70c4a5a6d7e8253f321bd2
O=C1c2c([nH]c3ccccc23)CCC1Cn1ccnc1
C-N(-C)-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[c:6]:[c:7]:[#7;a:8].[C;D1;H3:9]-[c:10]1:[#7;a:11]:[c:12]:[c:13]:[nH;D2;+0:14]:1>>[#7;a:8]:[c:7]:[c:6]-[C:4](=[O;D1;H0:5])-[C:2](-[CH2;D2;+0:1]-[n;H0;D3;+0:14]1:[c:13]:[c:12]:[#7;a:11]:[c:10]:1-[C;D1;H3:9])-[C:3]
97
[{"value": 96.4, "product": "CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.0, "product": "CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
3-[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride (10 g, 34 mmol) and 2-methylimidazole (16.8 g, 205 mmol, 6.0 eq.) were suspended in mixture of water (75 ml) and dimethyl formamide (37.5 ml). The reaction mixture was heated to reflux (102–103° C.) and stirred for a further 6 hours a...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
null
c1c[nH]cn1
c1ncc[nH]1
c1ncc[nH]1.C1[CH]CCc2[nH]c3ccccc3c21
Other
CN(C=O)C
null
6
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1>CN(C=O)C>Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4fddb17bac00436194745b17dd4dce0d
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1>>Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
Cl.CN(C)CC1CCC=2N(C3=CC=CC=C3C2C1=O)C.CC=1NC=CN1.O>>CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O
CN(C)[CH2:7][CH:8]1[CH2:9][CH2:10][c:11]2[c:12]([c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3[n:19]2[CH3:20])[C:21]1=[O:22].[CH3:1][c:2]1[n:3][cH:4][cH:5][nH:6]1>>[CH3:1][c:2]1[n:3][cH:4][cH:5][n:6]1[CH2:7][CH:8]1[CH2:9][CH2:10][c:11]2[c:12]([c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3[n:19]2[CH3:20])[C:21]1=[O:22]
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1
Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
baea70c3ed4e23fb3981a811d0c5d5797285f34961f974af088dbe9c4c60dd14
7c33147a6170e63e1fbe1110c4ce069481be57a96b70c4a5a6d7e8253f321bd2
O=C1c2c([nH]c3ccccc23)CCC1Cn1ccnc1
C-N(-C)-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[c:6]:[c:7]:[#7;a:8].[C;D1;H3:9]-[c:10]1:[#7;a:11]:[c:12]:[c:13]:[nH;D2;+0:14]:1>>[#7;a:8]:[c:7]:[c:6]-[C:4](=[O;D1;H0:5])-[C:2](-[CH2;D2;+0:1]-[n;H0;D3;+0:14]1:[c:13]:[c:12]:[#7;a:11]:[c:10]:1-[C;D1;H3:9])-[C:3]
83.1
[{"value": 83.0, "product": "CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.1, "product": "CC1=NC=CN1CC2CCC3=C(C=4C=CC=CC4N3C)C2=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
3-[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride (12 kg, 41 mol) and 2-methylimidazole (20.2 kg, 246 mol, 6 eq.) were suspended in mixture of water (120 L) and DMF (30 L). The reaction mixture was heated to reflux (100–102° C.) and stirred for 5 hours at this temperature. The reacti...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
null
c1c[nH]cn1
c1ncc[nH]1
c1ncc[nH]1.C1[CH]CCc2[nH]c3ccccc3c21
Other
CN(C)C=O
null
5
CN(C)CC1CCc2c(c3ccccc3n2C)C1=O.Cc1ncc[nH]1>CN(C)C=O>Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9b8e8ee433ae4003923410d0cc30e418
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1>>Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
ClC1=NC2=CC=CC=C2C(=N1)Cl.CC1=CC(=NN1)N>>ClC1=NC2=CC=CC=C2C(=N1)NC1=NNC(=C1)C
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:17][nH:18]1.Cl[c:6]1[n:7][c:8]([Cl:9])[n:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]12>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8]([Cl:9])[n:10][c:11]3[cH:12][cH:13][cH:14][cH:15][c:16]23)[n:17][nH:18]1
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1
Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
null
null
C(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc2c(Nc3cc[nH]n3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10]1:[#7;a:11]:[#7;a:12]:[c:13]:[c:14]:1>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10]2:[#7;a:11]:[#7;a:12]:[c:13]:[c:14]:2):[c:7]:1:[c:8]
null
[]
null
null
4
HOUR
To a solution of 2,4-dichloro-quinazoline (3.3 g, 16.6 mmol) in anhydrous ethanol (150 mL) is added 5-methyl-1H-pyrazol-3-yl amine (3.2 g, 32.9 mmol). The mixture is stirred at room temperature for 4 h, and the resulting precipitate is collected by filtration, washed with ethanol, and dried under vacuum to afford (2-ch...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1cn[nH]c1.c1ccc2ncncc2c1
HCl
C(C)O
null
4
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1>C(C)O>Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7f2377b602104b21a0f343502473fa9e
Nc1ncccc1C(=O)O.O=C(Cl)c1ccccc1C(F)(F)F>>O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12
FC(C1=C(C(=O)Cl)C=CC=C1)(F)F.NC1=C(C(=O)O)C=CC=N1.O>>FC(C1=C(C=CC=C1)C=1OC(C2=C(N1)N=CC=C2)=O)(F)F
[O:1]=[C:2]([OH:3])[c:21]1[c:16]([NH2:15])[n:17][cH:18][cH:19][cH:20]1.O=[C:4](Cl)[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[C:11]([F:12])([F:13])[F:14]>>[O:1]=[c:2]1[o:3][c:4](-[c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[n:15][c:16]2[n:17][cH:18][cH:19][cH:20][c:21]12
Nc1ncccc1C(=O)O.O=C(Cl)c1ccccc1C(F)(F)F
O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12
null
null
N1=CC=CC=C1
Aromatic Heterocycle Formation
OtherReaction
2dbd5bdc66d7edcd4601a60f389f4af1f471a8c5eb4f9da081529e62f2da61d0
bd3eed28c8485f0d5a54b9572c189e3c1ddb148eaacd326cd875cdab2e64ffc8
O=c1oc(-c2ccccc2)nc2ncccc12
Cl-[C;H0;D3;+0:1](=O)-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5](-[C:6](-[F;D1;H0:7])(-[F;D1;H0:8])-[F;D1;H0:9]):[c:10].[NH2;D1;+0:11]-[c:12](:[#7;a:13]:[c:14]):[c:15](-[C;H0;D3;+0:16](=[O;D1;H0:17])-[OH;D1;+0:18]):[c:19]>>[F;D1;H0:7]-[C:6](-[F;D1;H0:8])(-[F;D1;H0:9])-[c:5](:[c:10]):[c;H0;D3;+0:2](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:...
60
[{"value": 60.0, "product": "FC(C1=C(C=CC=C1)C=1OC(C2=C(N1)N=CC=C2)=O)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.4, "product": "FC(C1=C(C=CC=C1)C=1OC(C2=C(N1)N=CC=C2)=O)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-(Trifluoromethyl)benzoyl chloride (4.2 ml, 29.2 mmol) is added dropwise to a solution of 2-aminonicotinic acid (2.04 g, 14.76 mmol) in 20 ml of pyridine. The reaction mixture is heated at 158 C for 30 min then cooled to room temperature. The reaction is poured into 200 ml of water and an oil forms which solidifies up...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Carboxylic acid.Primary amine
null
c1ccncc1
c1nc2ncccc2co1
c1ccccc1.c1nc2ncccc2co1
HCl
N1=CC=CC=C1
null
null
Nc1ncccc1C(=O)O.O=C(Cl)c1ccccc1C(F)(F)F>N1=CC=CC=C1>O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9eb608089fd14276a75b55fb5c01adb8
O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12.[NH4+]>>NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F
FC(C1=C(C=CC=C1)C=1OC(C2=C(N1)N=CC=C2)=O)(F)F.[OH-].[NH4+]>>FC(C1=C(C(=O)NC2=C(C(=O)N)C=CC=N2)C=CC=C1)(F)F
[c:2]1(=[O:3])[c:4]2[cH:5][cH:6][cH:7][n:8][c:9]2[n:10][c:11](-[c:13]2[cH:14][cH:15][cH:16][cH:17][c:18]2[C:19]([F:20])([F:21])[F:22])[o:12]1.[NH4+:1]>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][n:8][c:9]1[NH:10][C:11](=[O:12])[c:13]1[cH:14][cH:15][cH:16][cH:17][c:18]1[C:19]([F:20])([F:21])[F:22]
O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12.[NH4+]
NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F
null
null
null
Functional Group Addition
OtherReaction
a6332fb803d8fc078e4dda8e27ec0146c21ce74941638af256736c803ace2b4c
962c8fe172bf467290cc03d27e3658940d6bee2d517209cffaa45b73a5cca1f8
O=C(Nc1ccccn1)c1ccccc1
[F;D1;H0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[c:5](:[c:6]):[c;H0;D3;+0:7](-[c;H0;D3;+0:8]1:[n;H0;D2;+0:9]:[c:10](:[#7;a:11]:[c:12]):[c:13](:[c:14]):[c;H0;D3;+0:15](=[O;D1;H0:16]):[o;H0;D2;+0:17]:1):[c:18]:[c:19].[NH4+;D0:20]>>[F;D1;H0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[c:5](:[c:6]):[c;H0;D3;+0:7](-[C;H0;D3;+0:8](=[...
33
[{"value": 33.0, "product": "FC(C1=C(C(=O)NC2=C(C(=O)N)C=CC=N2)C=CC=C1)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
2-(2-Trifluoromethyl-phenyl)-pyrido[2,3-d][1,3]oxazin-4-one (2.51 g) is stirred in 30% ammonium hydroxide (25 ml) at room temperature overnight. The resulting precipitate is filtered and rinsed with water and diethyl ether. The precipitate is dried under vacuum at 50 C overnight to give 2-(2-trifluoromethyl-benzoylamin...
10.6084/m9.figshare.5104873.v1
null
null
Primary amide.Secondary amide
c1nc2ncccc2co1
c1ccncc1
c1ccncc1.c1ccccc1
null
null
null
null
O=c1oc(-c2ccccc2C(F)(F)F)nc2ncccc12.[NH4+]>>NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ad07cb21f6bc41b9acab444e1cee39e1
NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F>>O=c1[nH]c(-c2ccccc2C(F)(F)F)nc2ncccc12
FC(C1=C(C(=O)NC2=C(C(=O)N)C=CC=N2)C=CC=C1)(F)F.[O-]CC.[K+].S(=O)(=O)(O)[O-].[Na+]>>FC(C1=C(C=CC=C1)C=1NC(C2=C(N1)N=CC=C2)=O)(F)F
O=[C:4]([c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[C:11]([F:12])([F:13])[F:14])[NH:15][c:16]1[n:17][cH:18][cH:19][cH:20][c:21]1[C:2](=[O:1])[NH2:3]>>[O:1]=[c:2]1[nH:3][c:4](-[c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[n:15][c:16]2[n:17][cH:18][cH:19][cH:20][c:21]12
NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F
O=c1[nH]c(-c2ccccc2C(F)(F)F)nc2ncccc12
null
null
O.C(C)O
Aromatic Heterocycle Formation
OtherReaction
e0ec58765b5a7ee3c266c0242348b15638d7e3c71f4e3b76437818b4ad2829ea
9d5aef0cada2072f52eb60b6996e8c9e376baa92104aa4e87786338b6493e605
O=c1[nH]c(-c2ccccc2)nc2ncccc12
O=[C;H0;D3;+0:1](-[NH;D2;+0:2]-[c:3](:[#7;a:4]:[c:5]):[c:6](-[C;H0;D3;+0:7](-[NH2;D1;+0:8])=[O;D1;H0:9]):[c:10])-[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:14](-[C:15](-[F;D1;H0:16])(-[F;D1;H0:17])-[F;D1;H0:18]):[c:19]>>[F;D1;H0:16]-[C:15](-[F;D1;H0:17])(-[F;D1;H0:18])-[c:14](:[c:19]):[c;H0;D3;+0:11](-[c;H0;D3;+0:1]1:[n;H0;D2;...
null
[]
null
null
null
null
2-(2-Trifluoromethyl-benzoylamino)-nicotinamide (800 mg, 2.6 mmol) is dissolved in 10 ml of ethanol. Potassium ethoxide (435 mg, 5.2 mmol) is added to the solution which is heated to reflux for 16 h. The reaction mixture is evaporated in vacuo to afford a gummy residue that is dissolved in water and acidified with 10% ...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Secondary amide
null
c1ccncc1
c1ncc2cccnc2n1
c1ccccc1.c1ncc2cccnc2n1
HO-
O.C(C)O
null
null
NC(=O)c1cccnc1NC(=O)c1ccccc1C(F)(F)F>O.C(C)O>O=c1[nH]c(-c2ccccc2C(F)(F)F)nc2ncccc12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c773c44bb45845f98c56eecf02d8c1d4
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1>>Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
BrC1=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C.C1(=CC=CC=C1)B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1
Br[c:12]1[cH:11][cH:10][c:9](-[c:8]2[n:7][c:6]([NH:5][c:4]3[cH:3][c:2]([CH3:1])[n:29][nH:28]3)[c:27]3[c:22]([n:21]2)[cH:23][cH:24][cH:25][cH:26]3)[cH:20][cH:19]1.OB(O)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8](-[c:9]3[cH:10][cH:11][c:12](-[c:13]4[cH:14][cH:15][cH:16][cH...
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1
Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
null
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
C1CCOC1.O
C-C Coupling
Suzuki coupling with boronic acids
d79a78c79f0c392f0911481acf5c300cc98205269acdb93c24fb610a61c4c868
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccc(-c3nc(Nc4ccn[nH]4)c4ccccc4n3)cc2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].O-B(-O)-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]>>[c:3]:[c:2]:[c;H0;D3;+0:1](-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:4]:[c:5]
51.4
[{"value": 51.0, "product": "C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.4, "product": "C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
Method H(i). To a mixture of [2-(4-bromo-phenyl)-quinazolin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amine (196 mg, 0.51 mmol) and phenylboronic acid (75 mg, 0.62 mmol) in THF/water (1/1, 4 mL) is added Na2CO3 (219 mg, 2.06 mmol), triphenylphosphine (9 mg, 1/15 mol %) and palladium acetate (1 mg, 1/135 mol %). The mixture is h...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccccc1
c1ccccc1.c1ccccc1
c1cn[nH]c1.c1ccccc1.c1ccccc1.c1ccc2ncncc2c1
HBr.B
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1CCOC1.O
80
null
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1>C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1CCOC1.O>Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4b1bcbd19517494f9bf9a403dd2b9886
CC1CCN(c2ccnc(Cl)n2)CC1.Cc1cc(N)[nH]n1>>Cc1cc(Nc2nccc(N3CCC(C)CC3)n2)[nH]n1
NC=1NN=C(C1)C.ClC1=NC=CC(=N1)N1CCC(CC1)C.C([O-])([O-])=O.[K+].[K+]>>CC1CCN(CC1)C1=NC(=NC=C1)NC=1NN=C(C1)C
Cl[c:6]1[n:7][cH:8][cH:9][c:10]([N:11]2[CH2:12][CH2:13][CH:14]([CH3:15])[CH2:16][CH2:17]2)[n:18]1.[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[nH:19][n:20]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][cH:8][cH:9][c:10]([N:11]3[CH2:12][CH2:13][CH:14]([CH3:15])[CH2:16][CH2:17]3)[n:18]2)[nH:19][n:20]1
CC1CCN(c2ccnc(Cl)n2)CC1.Cc1cc(N)[nH]n1
Cc1cc(Nc2nccc(N3CCC(C)CC3)n2)[nH]n1
null
null
C(CCC)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2nccc(N3CCCCC3)n2)[nH]n1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5].[NH2;D1;+0:6]-[c:7]1:[#7;a:8]:[#7;a:9]:[c:10]:[c:11]:1>>[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:6]-[c:7]1:[#7;a:8]:[#7;a:9]:[c:10]:[c:11]:1):[#7;a:4]:[c:5]
50
[{"value": 50.0, "product": "CC1CCN(CC1)C1=NC(=NC=C1)NC=1NN=C(C1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of 2-chloro-4-(4-methylpiperidin-1-yl)-pyrimidine (prepared using a procedure similar to the one reported in Eur. J. Med. Chem., 26(7) 729(1991))(222 mg, 1.05 mmol) in BuOH (5 mL) was added 3-amino-5-methyl-2H-pyrazole (305 mg, 3.15 mmol) and the reaction mixture was then heated under reflux overnight. Th...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cn[nH]c1.c1cncnc1.C1CC[NH]CC1
HCl
C(CCC)O
null
2
CC1CCN(c2ccnc(Cl)n2)CC1.Cc1cc(N)[nH]n1>C(CCC)O>Cc1cc(Nc2nccc(N3CCC(C)CC3)n2)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d802451e51154590a52dc727551dba05
Clc1ccccc1-c1nc(Cl)c2cccnc2n1.Nc1n[nH]c2c(F)cccc12>>Fc1cccc2c(Nc3nc(-c4ccccc4Cl)nc4ncccc34)n[nH]c12
ClC=1C2=C(N=C(N1)C1=C(C=CC=C1)Cl)N=CC=C2.FC=1C=CC=C2C(=NNC12)N>>ClC1=C(C=CC=C1)C=1N=C(C2=C(N1)N=CC=C2)NC2=NNC1=C(C=CC=C21)F
Cl[c:9]1[n:10][c:11](-[c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[Cl:18])[n:19][c:20]2[n:21][cH:22][cH:23][cH:24][c:25]12.[F:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]([NH2:8])[n:26][nH:27][c:28]12>>[F:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]([NH:8][c:9]3[n:10][c:11](-[c:12]4[cH:13][cH:14][cH:15][cH:16][c:17]4[Cl:18])[n:19][c:2...
Clc1ccccc1-c1nc(Cl)c2cccnc2n1.Nc1n[nH]c2c(F)cccc12
Fc1cccc2c(Nc3nc(-c4ccccc4Cl)nc4ncccc34)n[nH]c12
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
95363dd4f7eaf5ca3b2b81ca3d4d6901dabfa76417ca700d29bf339c0c5e8fb0
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2nc(Nc3n[nH]c4ccccc34)c3cccnc3n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[#7;a:6]:[c:7]):[c:8]:1:[c:9].[NH2;D1;+0:10]-[c:11]1:[#7;a:12]:[#7;a:13]:[c:14]:[c:15]:1>>[c:7]:[#7;a:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11]2:[#7;a:12]:[#7;a:13]:[c:14]:[c:15]:2):[c:8]:1:[c:9]
46
[{"value": 46.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Prepared from 4-Chloro-2-(2-chloro-phenyl)-pyrido[2,3-d]pyrimidine (100 mg, 0.36 mmol) and 7-Fluoro-1H-indazol-3-ylamine (108 mg, 0.72 mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (93 mg, 46% yield). HPLC-Method A, Rt 3.04 min; 1H NMR (DMSO, 500 MHz): δ 13.67 (1H, s), 11....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1ccccc1.c1cnc2ncncc2c1.c1ccc2n[nH]cc2c1
HCl
null
null
null
Clc1ccccc1-c1nc(Cl)c2cccnc2n1.Nc1n[nH]c2c(F)cccc12>>Fc1cccc2c(Nc3nc(-c4ccccc4Cl)nc4ncccc34)n[nH]c12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5c74c9c08b834259ac387d996b46fb8b
Clc1ccccc1-c1nc(Cl)c2ccncc2n1.Nc1n[nH]c2ccccc12>>Clc1ccccc1-c1nc(Nc2n[nH]c3ccccc23)c2ccncc2n1
ClC=1C2=C(N=C(N1)C1=C(C=CC=C1)Cl)C=NC=C2.N1N=C(C2=CC=CC=C12)N>>ClC1=C(C=CC=C1)C=1N=C(C2=C(N1)C=NC=C2)NC2=NNC1=CC=CC=C21
Cl[c:10]1[n:9][c:8](-[c:7]2[c:2]([Cl:1])[cH:3][cH:4][cH:5][cH:6]2)[n:27][c:26]2[c:21]1[cH:22][cH:23][n:24][cH:25]2.[NH2:11][c:12]1[n:13][nH:14][c:15]2[cH:16][cH:17][cH:18][cH:19][c:20]12>>[Cl:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1-[c:8]1[n:9][c:10]([NH:11][c:12]2[n:13][nH:14][c:15]3[cH:16][cH:17][cH:18][cH:19][c:20]23)...
Clc1ccccc1-c1nc(Cl)c2ccncc2n1.Nc1n[nH]c2ccccc12
Clc1ccccc1-c1nc(Nc2n[nH]c3ccccc23)c2ccncc2n1
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
d7e80981ec4355d1692da3210ded123ee4151f1f202c481ca7dd6b10037b54ac
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2nc(Nc3n[nH]c4ccccc34)c3ccncc3n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[c:9]:[c:10]:2:1.[NH2;D1;+0:11]-[c:12]1:[#7;a:13]:[#7;a:14]:[c:15]:[c:16]:1>>[#7;a:13]1:[#7;a:14]:[c:15]:[c:16]:[c:12]:1-[NH;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]2:[c:6]:[#7;a:7]:[c:8]:[c:9]:[c:10]:2:1
33
[{"value": 33.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Prepared from 4-Chloro-2-(2-chloro-phenyl)-pyrido[3,4-d]pyrimidine (100 mg, 0.36 mmol) and 1H-indazol-3-ylamine (88 mg, 0.66 mmol). Purification by preparative HPLC afforded the title compound as a yellow, di-TFA salt (72 mg, 33% yield). HPLC-Method A, Rt 3.21 min; 1H NMR (DMSO, 500 MHz): δ 12.95 (1H, s), 10.90 (1H, bs...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cc2cncnc2cn1
c1cc2cncnc2cn1
c1ccccc1.c1ccc2n[nH]cc2c1.c1cc2cncnc2cn1
HCl
null
null
null
Clc1ccccc1-c1nc(Cl)c2ccncc2n1.Nc1n[nH]c2ccccc12>>Clc1ccccc1-c1nc(Nc2n[nH]c3ccccc23)c2ccncc2n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b134537bc4c643eabbfe65a48bec7bec
COc1cccc2c(=O)[nH]c(-c3ccccc3C(F)(F)F)nc12.O=P(Cl)(Cl)Cl>>COc1cccc2c(Cl)nc(-c3ccccc3C(F)(F)F)nc12
COC=1C=CC=C2C(NC(=NC12)C1=C(C=CC=C1)C(F)(F)F)=O.Cl.C(C)N(CC)CC.O=P(Cl)(Cl)Cl>>ClC1=NC(=NC2=C(C=CC=C12)OC)C1=C(C=CC=C1)C(F)(F)F
O=[c:8]1[c:7]2[cH:6][cH:5][cH:4][c:3]([O:2][CH3:1])[c:23]2[n:22][c:11](-[c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[C:18]([F:19])([F:20])[F:21])[nH:10]1.O=P(Cl)(Cl)[Cl:9]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]([Cl:9])[n:10][c:11](-[c:12]3[cH:13][cH:14][cH:15][cH:16][c:17]3[C:18]([F:19])([F:20])[F:21])[n:22][c:...
COc1cccc2c(=O)[nH]c(-c3ccccc3C(F)(F)F)nc12.O=P(Cl)(Cl)Cl
COc1cccc2c(Cl)nc(-c3ccccc3C(F)(F)F)nc12
null
null
null
Functional Group Interconversion
OtherReaction
6f0285013e3068fc43dc9b72286fa243f9715611831aa1bdc0252411e07fdbf3
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(-c2ncc3ccccc3n2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4](-[c:5]):[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4](-[c:5]):[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]
89
[{"value": 89.0, "product": "ClC1=NC(=NC2=C(C=CC=C12)OC)C1=C(C=CC=C1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Prepared from 8-methoxy-2-(2-trifluoromethyl-phenyl)-3H-quinazolin-4-one (1.0 g, 3.12 mmol), triethylamine hydrochloride (472 mg, 3.43 mmol), and POCl3. Purification by flash chromatography afforded a white solid (89% yield). HPLC-Method A, Rt 4.10 min, (98%), MS (m/z) 258.08 (M+H). Conditions: See reaction.notes.proce...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ncc2ccccc2n1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
HCl
null
null
null
COc1cccc2c(=O)[nH]c(-c3ccccc3C(F)(F)F)nc12.O=P(Cl)(Cl)Cl>>COc1cccc2c(Cl)nc(-c3ccccc3C(F)(F)F)nc12
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3832c318a13546e6a68603f494b26d32
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1>>Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
BrC1=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C.C1(=CC=CC=C1)B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1
Br[c:12]1[cH:11][cH:10][c:9](-[c:8]2[n:7][c:6]([NH:5][c:4]3[cH:3][c:2]([CH3:1])[n:29][nH:28]3)[c:27]3[c:22]([n:21]2)[cH:23][cH:24][cH:25][cH:26]3)[cH:20][cH:19]1.OB(O)[c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8](-[c:9]3[cH:10][cH:11][c:12](-[c:13]4[cH:14][cH:15][cH:16][cH...
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1
Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
null
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
C1CCOC1.O
C-C Coupling
Suzuki coupling with boronic acids
d79a78c79f0c392f0911481acf5c300cc98205269acdb93c24fb610a61c4c868
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccc(-c3nc(Nc4ccn[nH]4)c4ccccc4n3)cc2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].O-B(-O)-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]>>[c:3]:[c:2]:[c;H0;D3;+0:1](-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:4]:[c:5]
51.4
[{"value": 51.0, "product": "C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.4, "product": "C1(=CC=C(C=C1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
To a mixture of [2-(4-bromo-phenyl)-quinazolin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amine (III-34) (196 mg, 0.51 mmol) and phenylboronic acid (75 mg, 0.62 mmol) in THF:water (1:1, 4 mL) was added Na2CO3 (219 mg, 2.06 mmol), triphenylphosphine (9 mg, 1/15 mol %) and palladium acetate (1 mg, 1:135 mol %). The resulting mixtu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccccc1
c1ccccc1.c1ccccc1
c1cn[nH]c1.c1ccccc1.c1ccccc1.c1ccc2ncncc2c1
HBr.B
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1CCOC1.O
80
null
Cc1cc(Nc2nc(-c3ccc(Br)cc3)nc3ccccc23)[nH]n1.OB(O)c1ccccc1>C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].C1CCOC1.O>Cc1cc(Nc2nc(-c3ccc(-c4ccccc4)cc3)nc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-033fb67cfd234c2db5036f5938eff4a9
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1>>Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
ClC1=NC2=CC=CC=C2C(=N1)Cl.CC1=CC(=NN1)N>>ClC1=NC2=CC=CC=C2C(=N1)NC1=NNC(=C1)C
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:17][nH:18]1.Cl[c:6]1[n:7][c:8]([Cl:9])[n:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]12>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8]([Cl:9])[n:10][c:11]3[cH:12][cH:13][cH:14][cH:15][c:16]23)[n:17][nH:18]1
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1
Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
null
null
C(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc2c(Nc3cc[nH]n3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10]1:[#7;a:11]:[#7;a:12]:[c:13]:[c:14]:1>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10]2:[#7;a:11]:[#7;a:12]:[c:13]:[c:14]:2):[c:7]:1:[c:8]
93
[{"value": 93.0, "product": "ClC1=NC2=CC=CC=C2C(=N1)NC1=NNC(=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.8, "product": "ClC1=NC2=CC=CC=C2C(=N1)NC1=NNC(=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
A suspension of 1H-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POCl3 (60 mL, 644 mmol) and N,N-dimethylaniline (8 mL, 63.1 mmol) was heated under reflux for 2 h. The excess POCl3 was removed in vacuo, the residue poured into ice, and the resulting precipitate collected by filtration. The crude solid product 2,4-dichlo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1cn[nH]c1.c1ccc2ncncc2c1
HCl
C(C)O
null
4
Cc1cc(N)n[nH]1.Clc1nc(Cl)c2ccccc2n1>C(C)O>Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d722e543915a4c2da4ccb700d9ffdc57
Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1.Cc1cccc(B(O)O)c1>>Cc1cccc(-c2nc(Nc3cc(C)n[nH]3)c3ccccc3n2)c1
ClC1=NC2=CC=CC=C2C(=N1)NC1=NNC(=C1)C.C1(=CC(=CC=C1)B(O)O)C.C(=O)([O-])[O-].[Na+].[Na+].C(C)(C)(C)P(C(C)(C)C)C(C)(C)C>>CC=1C=C(C=CC1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C
Cl[c:7]1[n:8][c:9]([NH:10][c:11]2[cH:12][c:13]([CH3:14])[nH:15][n:16]2)[c:17]2[cH:18][cH:19][cH:20][cH:21][c:22]2[n:23]1.OB(O)[c:6]1[cH:5][cH:4][cH:3][c:2]([CH3:1])[cH:24]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6](-[c:7]2[n:8][c:9]([NH:10][c:11]3[cH:12][c:13]([CH3:14])[n:15][nH:16]3)[c:17]3[cH:18][cH:19][cH:20][cH:21][c:2...
Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1.Cc1cccc(B(O)O)c1
Cc1cccc(-c2nc(Nc3cc(C)n[nH]3)c3ccccc3n2)c1
null
C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl.[Fe+2]
O.CN(C)C=O
C-C Coupling
OtherReaction
e11757e18e26f9674938ea5830aa7b8b9ca2f4d52a63db4dc23ddf9cfe7f2462
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2nc(Nc3ccn[nH]3)c3ccccc3n2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]-[#7:6]-[c:7]1:[c:8]:[c:9](-[C;D1;H3:10]):[nH;D2;+0:11]:[n;H0;D2;+0:12]:1.O-B(-O)-[c;H0;D3;+0:13](:[c:14]:[c:15]):[c:16]:[c:17]>>[C;D1;H3:10]-[c:9]1:[c:8]:[c:7](-[#7:6]-[c:5]:[#7;a:4]:[c;H0;D3;+0:1](-[c;H0;D3;+0:13](:[c:14]:[c:15]):[c:16]:[c:17]):[#7;a:2]:[c:3]):[nH;D2;+...
101.8
[{"value": 75.0, "product": "CC=1C=C(C=CC1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 101.8, "product": "CC=1C=C(C=CC1)C1=NC2=CC=CC=C2C(=N1)NC=1NN=C(C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A suspension of 1H-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POCl3 (60 mL, 644 mmol) and N,N-dimethylaniline (8 mL, 63.1 mmol) was heated under reflux for 2 h. The excess POCl3 was removed in vacuo, the residue poured into ice, and the resulting precipitate collected by filtration. The crude solid product 2,4-dichlo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccc2ncncc2c1.c1ccccc1
c1ccccc1.c1ccc2ncncc2c1
c1ccccc1.c1cn[nH]c1.c1ccc2ncncc2c1
HCl.B
C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl.[Fe+2].O.CN(C)C=O
80
null
Cc1cc(Nc2nc(Cl)nc3ccccc23)n[nH]1.Cc1cccc(B(O)O)c1>C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P([C-]2C=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl.[Fe+2].O.CN(C)C=O>Cc1cccc(-c2nc(Nc3cc(C)n[nH]3)c3ccccc3n2)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2c4aae8e65dc4453b9a093bb758a2995
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>>O=C(O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
COC(=O)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1.[OH-].[Na+].Cl>>C(=O)(O)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1
C[O:3][C:2](=[O:1])[c:4]1[cH:5][c:6]([NH:7][c:8]2[n:9][c:10](-[c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[n:17][c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]23)[nH:24][n:25]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[n:9][c:10](-[c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[n:17][c:18]3[cH:19][cH:20][cH:21][cH:22][...
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
O=C(O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
null
null
null
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(-c2nc(Nc3ccn[nH]3)c3ccccc3n2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5]:[#7;a:6]>>[#7;a:6]:[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
94.2
[{"value": 94.0, "product": "C(=O)(O)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.2, "product": "C(=O)(O)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
5
HOUR
(5-Methoxycarbonyl-2H-pyrazol-3-yl)-(2-phenyl-quinazolin-4-yl)-amine (III-73) (345 mg, 1 mmole in THF, 6 mL) was treated with NaOH (1M, 4.0 mL), stirred at 50° C. for 5 hours, cooled to room temperature, and neutralised with 1M HCl. The mixture was concentrated in vacuo to remove THF then diluted with water and the res...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cn[nH]c1.c1ccccc1.c1ccc2ncncc2c1
Other
null
50
5
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>>O=C(O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-8f6d4d2b6d544574b77ff5bfc8e3f093
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>>OCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
C(O)([O-])=O.[Na+].Cl.COC(=O)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1.[BH4-].[Li+]>>OCC=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1
CO[C:2](=[O:1])[c:3]1[cH:4][c:5]([NH:6][c:7]2[n:8][c:9](-[c:10]3[cH:11][cH:12][cH:13][cH:14][cH:15]3)[n:16][c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]23)[nH:23][n:24]1>>[OH:1][CH2:2][c:3]1[cH:4][c:5]([NH:6][c:7]2[n:8][c:9](-[c:10]3[cH:11][cH:12][cH:13][cH:14][cH:15]3)[n:16][c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]23)[nH:...
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
OCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
null
null
C1CCOC1.C(C)(=O)OCC
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
c1ccc(-c2nc(Nc3ccn[nH]3)c3ccccc3n2)cc1
C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[c:3]1:[#7;a:4]:[#7;a:5]:[c:6]:[c:7]:1>>[OH;D1;+0:2]-[CH2;D2;+0:1]-[c:3]1:[#7;a:4]:[#7;a:5]:[c:6]:[c:7]:1
null
[]
null
null
null
null
A solution of (5-Methoxycarbonyl-2H-pyrazol-3-yl)-(2-phenyl-quinazolin-4-yl)-amine (III-73) (345 mg, 1 mmol) in anhydrous THF (10 mL) was treated with lithium borohydride (125 mg, 5.75 mmol) at 65° C. for 5 hours. The mixture was cooled to room temperature then combined with 2M HCl and ethyl acetate. Solid sodium hydro...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
c1cn[nH]c1.c1ccccc1.c1ccc2ncncc2c1
Other
C1CCOC1.C(C)(=O)OCC
null
null
COC(=O)c1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>C1CCOC1.C(C)(=O)OCC>OCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c3de370c8f6940959561675cc6d590bf
CC(C)(C)OC(=O)NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>>NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
C(C)(C)(C)OC(=O)NCCCC=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1.C(=O)(C(F)(F)F)O>>NCCCC=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1
CC(C)(C)OC(=O)[NH:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][c:7]([NH:8][c:9]2[n:10][c:11](-[c:12]3[cH:13][cH:14][cH:15][cH:16][cH:17]3)[n:18][c:19]3[cH:20][cH:21][cH:22][cH:23][c:24]23)[nH:25][n:26]1>>[NH2:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][c:7]([NH:8][c:9]2[n:10][c:11](-[c:12]3[cH:13][cH:14][cH:15][cH:16][cH:17]3)[n:18][c:...
CC(C)(C)OC(=O)NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
null
null
ClCCl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccc(-c2nc(Nc3ccn[nH]3)c3ccccc3n2)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[C:3]>>[C:3]-[C:2]-[NH2;D1;+0:1]
63.3
[{"value": 63.0, "product": "NCCCC=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.3, "product": "NCCCC=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of [5-(3-tert-butoxycarbonylaminoprop-1-yl)-2H-pyrazol-3-yl]-(2-phenyl-quinazolin-4-yl)-amine (III-80) (250 mg, 0.56 mmol), in dichloromethane (3 mL) at 0° C. was treated with TFA (2 mL). The mixture was warmed to room temperature then concentrated in vacuo. The residue was triturated and concentrated from d...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1cn[nH]c1.c1ccccc1.c1ccc2ncncc2c1
HO-
ClCCl
null
null
CC(C)(C)OC(=O)NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1>ClCCl>NCCCc1cc(Nc2nc(-c3ccccc3)nc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c7a7c6e1b27b425197b7322315a00e4d
CC1CCNCC1.Clc1nc(Nc2cc(C3CC3)[nH]n2)c2ccccc2n1>>CC1CCN(c2nc(Nc3cc(C4CC4)n[nH]3)c3ccccc3n2)CC1
C([O-])([O-])=O.[K+].[K+].C1(CC1)C1=CC(=NN1)NC1=NC(=NC2=CC=CC=C12)Cl.CC1CCNCC1>>C1(CC1)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)N1CCC(CC1)C
[CH3:1][CH:2]1[CH2:3][CH2:4][NH:5][CH2:25][CH2:26]1.Cl[c:6]1[n:7][c:8]([NH:9][c:10]2[cH:11][c:12]([CH:13]3[CH2:14][CH2:15]3)[nH:16][n:17]2)[c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]2[n:24]1>>[CH3:1][CH:2]1[CH2:3][CH2:4][N:5]([c:6]2[n:7][c:8]([NH:9][c:10]3[cH:11][c:12]([CH:13]4[CH2:14][CH2:15]4)[n:16][nH:17]3)[c:18]3[cH:...
CC1CCNCC1.Clc1nc(Nc2cc(C3CC3)[nH]n2)c2ccccc2n1
CC1CCN(c2nc(Nc3cc(C4CC4)n[nH]3)c3ccccc3n2)CC1
null
null
C(C)(C)(C)O
Heteroatom Alkylation and Arylation
OtherReaction
2d4d37ff2a13382a8cb5903cac2202616d5c68a02b154ba28452de35ced25a57
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc2c(Nc3cc(C4CC4)n[nH]3)nc(N3CCCCC3)nc2c1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[#7;a:4]:[c:5]-[#7:6]-[c:7]1:[c:8]:[c:9](-[C:10]):[nH;D2;+0:11]:[n;H0;D2;+0:12]:1.[C:13]-[C:14]-[NH;D2;+0:15]-[C:16]-[C:17]>>[C:10]-[c:9]1:[c:8]:[c:7](-[#7:6]-[c:5]:[#7;a:4]:[c;H0;D3;+0:1](-[N;H0;D3;+0:15](-[C:14]-[C:13])-[C:16]-[C:17]):[#7;a:2]:[c:3]):[nH;D2;+0:12]:[n;H0;D2;+0:11]:1
86.1
[{"value": 85.0, "product": "C1(CC1)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)N1CCC(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.1, "product": "C1(CC1)C=1C=C(NN1)NC1=NC(=NC2=CC=CC=C12)N1CCC(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (5-cyclopropyl-1H-pyrazol-3-yl)-(2-chloro-quinazolin-4-yl)-amine (118 mg, 0.41 mmol) in tert-butanol (3.0 mL) was added 4-methylpiperidine (0.49 mL, 4.1 mmol) and the reaction mixture heated at reflux overnight. The reaction mixture was concentrated in vacuo and the residue dissolved in a mixture EtOH:...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNCC1.c1ccc2ncncc2c1
C1CC[NH]CC1.c1ccc2ncncc2c1
C1CC[NH]CC1.c1cn[nH]c1.C1CC1.c1ccc2ncncc2c1
HCl
C(C)(C)(C)O
null
2
CC1CCNCC1.Clc1nc(Nc2cc(C3CC3)[nH]n2)c2ccccc2n1>C(C)(C)(C)O>CC1CCN(c2nc(Nc3cc(C4CC4)n[nH]3)c3ccccc3n2)CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-112cf652bf9f4a6688b28ac649f63860
Cc1cc(N)n[nH]1.Clc1cc(Cl)nc(-c2ccccc2)n1>>Cc1cc(Nc2cc(Cl)nc(-c3ccccc3)n2)[nH]n1
C=1C=CC(=CC1)C=2N=C(C=C(N2)Cl)Cl.NC1=NNC(=C1)C.C(C)(C)N(C(C)C)CC.[I-].[Na+]>>ClC1=CC(=NC(=N1)C1=CC=CC=C1)NC=1NN=C(C1)C
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:19][nH:20]1.Cl[c:6]1[cH:7][c:8]([Cl:9])[n:10][c:11](-[c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[n:18]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[cH:7][c:8]([Cl:9])[n:10][c:11](-[c:12]3[cH:13][cH:14][cH:15][cH:16][cH:17]3)[n:18]2)[nH:19][n:20]1
Cc1cc(N)n[nH]1.Clc1cc(Cl)nc(-c2ccccc2)n1
Cc1cc(Nc2cc(Cl)nc(-c3ccccc3)n2)[nH]n1
null
null
C(CCC)O
Heteroatom Alkylation and Arylation
OtherReaction
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2nccc(Nc3ccn[nH]3)n2)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.[C;D1;H3:9]-[c:10]1:[c:11]:[c:12](-[NH2;D1;+0:13]):[n;H0;D2;+0:14]:[nH;D2;+0:15]:1>>[C;D1;H3:9]-[c:10]1:[c:11]:[c:12](-[NH;D2;+0:13]-[c;H0;D3;+0:1]2:[#7;a:2]:[c:3](-[c:4]):[#7;a:5]:[c:6](-[Cl;D1;H0:7]):[c:8]:2):[nH;D2;+0:14]:[n;H0;D2;+0:15]...
29.4
[{"value": 29.0, "product": "ClC1=CC(=NC(=N1)C1=CC=CC=C1)NC=1NN=C(C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.4, "product": "ClC1=CC(=NC(=N1)C1=CC=CC=C1)NC=1NN=C(C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
117
CELSIUS
null
null
A suspension of Fenclorim (4,6-dichloro-2-phenylpyrimidine)(0.1 g, 0.44 mmol), 3-amino-5-methylpyrazole (0.045 g, 0.47 mmol), N,N-diisopropylethylamine (0.08 ml, 0.47 mmol) and sodium iodide (0.067 g, 0.44 mmol) in n-butanol (5 ml) were heated at 117° C. for 18 hours. The solvent was removed in vacuo and the crude prod...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cn[nH]c1.c1cncnc1.c1ccccc1
HCl
C(CCC)O
117
null
Cc1cc(N)n[nH]1.Clc1cc(Cl)nc(-c2ccccc2)n1>C(CCC)O>Cc1cc(Nc2cc(Cl)nc(-c3ccccc3)n2)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-74bd5f909fdd45cab060be5e2f1707cd
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)nc2ncccc12>>Cc1cc(Nc2nc(-c3ccccc3)nc3ncccc23)[nH]n1
ClC=1C2=C(N=C(N1)C1=CC=CC=C1)N=CC=C2.NC1=NNC(=C1)C>>CC=1C=C(NN1)NC=1C2=C(N=C(N1)C1=CC=CC=C1)N=CC=C2
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:22][nH:23]1.Cl[c:6]1[n:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[n:15][c:16]2[n:17][cH:18][cH:19][cH:20][c:21]12>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8](-[c:9]3[cH:10][cH:11][cH:12][cH:13][cH:14]3)[n:15][c:16]3[n:17][cH:18][cH:19][cH:20][c:21]23)[nH:22][n:23]1
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)nc2ncccc12
Cc1cc(Nc2nc(-c3ccccc3)nc3ncccc23)[nH]n1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
95363dd4f7eaf5ca3b2b81ca3d4d6901dabfa76417ca700d29bf339c0c5e8fb0
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2nc(Nc3ccn[nH]3)c3cccnc3n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[#7;a:6]:[c:7]):[c:8]:1:[c:9].[C;D1;H3:10]-[c:11]1:[c:12]:[c:13](-[NH2;D1;+0:14]):[n;H0;D2;+0:15]:[nH;D2;+0:16]:1>>[C;D1;H3:10]-[c:11]1:[c:12]:[c:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]2:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[#7;a:6]:[c:7]):[c:8]:2:[c:9]):[nH;D2;+0:15]:[n;H0;D2;+0:1...
50.7
[{"value": 50.0, "product": "CC=1C=C(NN1)NC=1C2=C(N=C(N1)C1=CC=CC=C1)N=CC=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 50.7, "product": "CC=1C=C(NN1)NC=1C2=C(N=C(N1)C1=CC=CC=C1)N=CC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
null
null
To a solution of 4-chloro-2-phenyl-pyrido[2,3-d]pyrimidine (J. Pharm. Belg., 29, 1974, 145–148) (109 mg, 0.45 mmol) in THF (15 mL) was added 3-amino-5-methyl pyrazole (48 mg, 0.5 mmol) and the resulting mixture heated at 65° C. overnight. The mixture was cooled to room temperature and the resulting suspension was filte...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cnc2ncncc2c1
c1cnc2ncncc2c1
c1cn[nH]c1.c1ccccc1.c1cnc2ncncc2c1
HCl
C1CCOC1
65
null
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)nc2ncccc12>C1CCOC1>Cc1cc(Nc2nc(-c3ccccc3)nc3ncccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1df214bd9a1d4ad4b0661807b2b55fd6
Cc1cc(N)n[nH]1.ClC1=NC2(Cl)N=CN=C2C=N1>>Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1
ClC=1N=CC2=NC=NC2(N1)Cl.CC1=CC(=NN1)N>>ClC=1N=CC2=NC=NC2(N1)NC1=NNC(=C1)C
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:16][nH:17]1.Cl[C:6]12[N:7]=[CH:8][N:9]=[C:10]1[CH:11]=[N:12][C:13]([Cl:14])=[N:15]2>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][C:6]23[N:7]=[CH:8][N:9]=[C:10]2[CH:11]=[N:12][C:13]([Cl:14])=[N:15]3)[n:16][nH:17]1
Cc1cc(N)n[nH]1.ClC1=NC2(Cl)N=CN=C2C=N1
Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1
null
null
C(C)O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
9f6414acc7dc8d92deef57b71c36c65409f27886ed6c04cda812b2c2b3e36d96
eea9a5e587609dc5fd77390cd39192bf408374166fb31275d4a6d328d3b38b84
C1=NC=NC2(Nc3cc[nH]n3)N=CN=C12
Cl-[C;H0;D4;+0:1]12-[#7:2]=[C:3](-[Cl;D1;H0:4])-[#7:5]=[C:6]-[C:7]-1=[#7:8]-[C:9]=[#7:10]-2.[NH2;D1;+0:11]-[c:12]1:[#7;a:13]:[#7;a:14]:[c:15]:[c:16]:1>>[Cl;D1;H0:4]-[C:3]1=[#7:2]-[C;H0;D4;+0:1]2(-[NH;D2;+0:11]-[c:12]3:[#7;a:13]:[#7;a:14]:[c:15]:[c:16]:3)-[#7:10]=[C:9]-[#7:8]=[C:7]-2-[C:6]=[#7:5]-1
58
[{"value": 58.0, "product": "ClC=1N=CC2=NC=NC2(N1)NC1=NNC(=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.6, "product": "ClC=1N=CC2=NC=NC2(N1)NC1=NNC(=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
48
HOUR
To a suspension of 2,4-dichloro-purine (2.0 g, 10.6 mmol) in anhydrous ethanol (10 mL) was added 5-methyl-1H-pyrazol-3-yl amine (2.05 g, 21.2 mmol). The resulting mixture was stirred at room temperature for 48 h. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to affor...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Primary amine
Secondary amine
C1=NC=NC2N=CN=C12
C1=NC=NC2N=CN=C12
c1cn[nH]c1.C1=NC=NC2N=CN=C12
HCl
C(C)O
null
48
Cc1cc(N)n[nH]1.ClC1=NC2(Cl)N=CN=C2C=N1>C(C)O>Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-033fb5014fbd4547a14bf5c0235026b0
CC1CCNCC1.Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1>>Cc1cc(NC23N=CN=C2C=NC(N2CCC(C)CC2)=N3)[nH]n1
ClC=1N=CC2=NC=NC2(N1)NC1=NNC(=C1)C.CC1CCNCC1.C([O-])([O-])=O.[K+].[K+]>>CC1CCN(CC1)C=1N=CC2=NC=NC2(N1)NC=1NN=C(C1)C
[NH:14]1[CH2:15][CH2:16][CH:17]([CH3:18])[CH2:19][CH2:20]1.Cl[C:13]1=[N:21][C:6]2([NH:5][c:4]3[cH:3][c:2]([CH3:1])[nH:23][n:22]3)[N:7]=[CH:8][N:9]=[C:10]2[CH:11]=[N:12]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][C:6]23[N:7]=[CH:8][N:9]=[C:10]2[CH:11]=[N:12][C:13]([N:14]2[CH2:15][CH2:16][CH:17]([CH3:18])[CH2:19][CH2:20]2)=[N:21]...
CC1CCNCC1.Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1
Cc1cc(NC23N=CN=C2C=NC(N2CCC(C)CC2)=N3)[nH]n1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
bd107ca2f0c4326411f18bbf4c383fd979f0c194e59e94f098fb780e597038c5
f42712f62a63a0590ff88b97f02f7ce55443e44af887e4114dc924862f99ddaa
C1=NC(N2CCCCC2)=NC2(Nc3ccn[nH]3)N=CN=C12
Cl-[C;H0;D3;+0:1]1=[#7:2]-[C:3](-[#7:4]-[c:5]2:[c:6]:[c:7](-[C;D1;H3:8]):[nH;D2;+0:9]:[n;H0;D2;+0:10]:2)(-[#7:11])-[C:12](=[#7:13])-[C:14]=[#7:15]-1.[C:16]-[C:17]-[NH;D2;+0:18]-[C:19]-[C:20]>>[#7:11]-[C:3]1(-[#7:4]-[c:5]2:[c:6]:[c:7](-[C;D1;H3:8]):[n;H0;D2;+0:9]:[nH;D2;+0:10]:2)-[#7:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:18](-...
90
[{"value": 90.0, "product": "CC1CCN(CC1)C=1N=CC2=NC=NC2(N1)NC=1NN=C(C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.0, "product": "CC1CCN(CC1)C=1N=CC2=NC=NC2(N1)NC=1NN=C(C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a suspension of 2,4-dichloro-purine (2.0 g, 10.6 mmol) in anhydrous ethanol (10 mL) was added 5-methyl-1H-pyrazol-3-yl amine (2.05 g, 21.2 mmol). The resulting mixture was stirred at room temperature for 48 h. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to affor...
10.6084/m9.figshare.5104873.v1
null
Alkenyl halide.Substituted imine.Secondary amine
Substituted imine.Tertiary amine
C1CCNCC1.C1=NC=NC2N=CN=C12
C1=NC=NC2N=CN=C12.C1CC[NH]CC1
c1cn[nH]c1.C1=NC=NC2N=CN=C12.C1CC[NH]CC1
HCl
null
null
2
CC1CCNCC1.Cc1cc(NC23N=CN=C2C=NC(Cl)=N3)n[nH]1>>Cc1cc(NC23N=CN=C2C=NC(N2CCC(C)CC2)=N3)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-90706312daec4ca2b316204aeffe5753
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)cc2ccccc12>>Cc1cc(Nc2nc(-c3ccccc3)cc3ccccc23)[nH]n1
ClC1=NC(=CC2=CC=CC=C12)C1=CC=CC=C1.NC1=NNC(=C1)C.C([O-])([O-])=O.[K+].[K+]>>CC=1C=C(NN1)NC1=NC(=CC2=CC=CC=C12)C1=CC=CC=C1
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[n:22][nH:23]1.Cl[c:6]1[n:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[cH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21]12>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][c:8](-[c:9]3[cH:10][cH:11][cH:12][cH:13][cH:14]3)[cH:15][c:16]3[cH:17][cH:18][cH:19][cH:20][c:21]23)[nH:22][n:23]1
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)cc2ccccc12
Cc1cc(Nc2nc(-c3ccccc3)cc3ccccc23)[nH]n1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
17c3dbb58f19c559a89452c2c52a32d81319b5dd6d11e225611cc478eba61c1b
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2cc3ccccc3c(Nc3ccn[nH]3)n2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](:[c:5]):[c:6].[C;D1;H3:7]-[c:8]1:[c:9]:[c:10](-[NH2;D1;+0:11]):[n;H0;D2;+0:12]:[nH;D2;+0:13]:1>>[C;D1;H3:7]-[c:8]1:[c:9]:[c:10](-[NH;D2;+0:11]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](:[c:5]):[c:6]):[nH;D2;+0:12]:[n;H0;D2;+0:13]:1
null
[]
null
null
null
null
To a solution of 1-chloro-3-phenylisoquinoline (J. Het. Chem., 20, 1983, 121–128)(0.33 g, 1.37 mmol) in DMF (anhydrous, 5 mL) was added 3-amino-5-methylpyrazole (0.27 g, 2.74 mmol) and potassium carbonate (0.57 g, 4.13 mmol) and the resulting mixture was heated at reflux for 6 hours. The reaction mixture was then coole...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2cnccc2c1
c1ccc2cnccc2c1
c1cn[nH]c1.c1ccccc1.c1ccc2cnccc2c1
HCl
CN(C)C=O
null
null
Cc1cc(N)n[nH]1.Clc1nc(-c2ccccc2)cc2ccccc12>CN(C)C=O>Cc1cc(Nc2nc(-c3ccccc3)cc3ccccc23)[nH]n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-020440c00af440c8b9cd3a3777146cf3
FC(F)(F)c1ccccc1-c1cc2ccccc2c(Cl)n1.Nc1n[nH]c2ccccc12>>FC(F)(F)c1ccccc1-c1cc2ccccc2c(Nc2n[nH]c3ccccc23)n1
ClC1=NC(=CC2=CC=CC=C12)C1=C(C=CC=C1)C(F)(F)F.N1N=C(C2=CC=CC=C12)N>>N1N=C(C2=CC=CC=C12)NC1=NC(=CC2=CC=CC=C12)C1=C(C=CC=C1)C(F)(F)F
Cl[c:19]1[c:18]2[c:13]([cH:12][c:11](-[c:10]3[c:5]([C:2]([F:1])([F:3])[F:4])[cH:6][cH:7][cH:8][cH:9]3)[n:30]1)[cH:14][cH:15][cH:16][cH:17]2.[NH2:20][c:21]1[n:22][nH:23][c:24]2[cH:25][cH:26][cH:27][cH:28][c:29]12>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1-[c:11]1[cH:12][c:13]2[cH:14][cH:15][cH:16][cH...
FC(F)(F)c1ccccc1-c1cc2ccccc2c(Cl)n1.Nc1n[nH]c2ccccc12
FC(F)(F)c1ccccc1-c1cc2ccccc2c(Nc2n[nH]c3ccccc23)n1
null
null
C(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
17c3dbb58f19c559a89452c2c52a32d81319b5dd6d11e225611cc478eba61c1b
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(-c2cc3ccccc3c(Nc3n[nH]c4ccccc34)n2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8]1:[#7;a:9]:[#7;a:10]:[c:11]:[c:12]:1>>[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:7]-[c:8]1:[#7;a:9]:[#7;a:10]:[c:11]:[c:12]:1):[c:4](:[c:5]):[c:6]
27
[{"value": 27.0, "product": "N1N=C(C2=CC=CC=C12)NC1=NC(=CC2=CC=CC=C12)C1=C(C=CC=C1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 26.5, "product": "N1N=C(C2=CC=CC=C12)NC1=NC(=CC2=CC=CC=C12)C1=C(C=CC=C1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 1-chloro-3-(2-trifluoromethyl-phenyl)-isoquinoline (100 mg, 0.326 mmol) and 1H-indazol-3-ylamine (86 mg, 0.651 mmol) in ethanol (3 mL) was heated at 160 C and the solvent evaporated with a stream of nitrogen. The remaining oil was then heated at 160 C for 18 hours under nitrogen. The resulting melt was di...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2cnccc2c1
c1ccc2cnccc2c1
c1ccccc1.c1ccc2cnccc2c1.c1ccc2n[nH]cc2c1
HCl
C(C)O
null
null
FC(F)(F)c1ccccc1-c1cc2ccccc2c(Cl)n1.Nc1n[nH]c2ccccc12>C(C)O>FC(F)(F)c1ccccc1-c1cc2ccccc2c(Nc2n[nH]c3ccccc23)n1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d2bf217eddca4257ae51da4d5cb2c928
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>>CC(C)(C)OC(=O)N(Cc1ccc(C(=O)O)cc1)Cc1ccccn1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C(=O)OC)C=C1.CO.[OH-].[Na+]>>C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C(=O)O)C=C1
C[O:16][C:14]([c:13]1[cH:12][cH:11][c:10]([CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:19][c:20]2[cH:21][cH:22][cH:23][cH:24][n:25]2)[cH:18][cH:17]1)=[O:15]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([CH2:9][c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[OH:16])[cH:17][cH:18]1)[CH2:19][c:2...
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1
CC(C)(C)OC(=O)N(Cc1ccc(C(=O)O)cc1)Cc1ccccn1
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(CNCc2ccccn2)cc1
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]
63.9
[{"value": 63.9, "product": "C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C(=O)O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
DAY
The compound obtained in Example 1-1 (200.6 mg) was added with methanol (2 ml), THF (2 ml), and 1 mol/l aqueous solution of sodium hydroxide (2 ml), and the mixture was stirred for one day at room temperature. After the completion of the reaction, the solvent was removed by distillation and water (5 ml) was added. Aque...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccncc1
Other
C1CCOC1
null
24
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>C1CCOC1>CC(C)(C)OC(=O)N(Cc1ccc(C(=O)O)cc1)Cc1ccccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-639408831de942e6a598272ed67cc92c
COC(=O)Cc1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>>CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)O)cc1)Cc1ccccn1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C=C1)CC(=O)OC.[OH-].[Na+]>>C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C=C1)CC(=O)O
C[O:17][C:15]([CH2:14][c:13]1[cH:12][cH:11][c:10]([CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:20][c:21]2[cH:22][cH:23][cH:24][cH:25][n:26]2)[cH:19][cH:18]1)=[O:16]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([CH2:9][c:10]1[cH:11][cH:12][c:13]([CH2:14][C:15](=[O:16])[OH:17])[cH:18][cH:1...
COC(=O)Cc1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1
CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)O)cc1)Cc1ccccn1
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(CNCc2ccccn2)cc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
98.3
[{"value": 98.3, "product": "C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C=C1)CC(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
35
MINUTE
The compound obtained in Example 8-3 (83.2 mg) was dissolved in THF (0.8 ml) and methanol (0.8 ml). After the addition of 1 N aqueous solution of sodium hydroxide (0.8 ml), the mixture was stirred for 35 minutes at room temperature. After the reaction, the solvent was removed by distillation and the residue was dissolv...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccncc1
Other
CO.C1CCOC1
null
0.583333
COC(=O)Cc1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>CO.C1CCOC1>CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)O)cc1)Cc1ccccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5fa1bf7313374de8b97081467abfed33
O=C(NCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)OCc1ccccc1>>N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
C(=O)(OCC1C2=CC=CC=C2C2=CC=CC=C12)N[C@@H](CCCNC(=O)OCC1=CC=CC=C1)C(=O)O.C(C)NCC>>C(=O)(OCC1=CC=CC=C1)NCCC[C@H](N)C(=O)O
O=C(OCC1c2ccccc2-c2ccccc21)[NH:1][C@@H:2]([CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:8])[O:9][CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1)[C:17](=[O:18])[OH:19]>>[NH2:1][C@@H:2]([CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:8])[O:9][CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1)[C:17](=[O:18])[OH:19]
O=C(NCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)OCc1ccccc1
N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
null
null
CN(C)C=O
Reduction
Hydrogenolysis of amides/imides/carbamates
6b8c76d50ec667b483b13f7e325104eed6ba06fddb821da46e405c5dce0a3de5
4e549866ec1acadec4c84aaf8495992a28ec78d8ea5ef1b9f44dd843b0dcb7d4
c1ccccc1
O=C(-O-C-C1-c2:c:c:c:c:c:2-c2:c:c:c:c:c:2-1)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[O;D1;H1:6]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4](=[O;D1;H0:5])-[O;D1;H1:6]
199.4
[{"value": 199.4, "product": "C(=O)(OCC1=CC=CC=C1)NCCC[C@H](N)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
The compound obtained in Example 8-5 (122.8 mg) was dissolved in DMF (2.6 ml). After the addition of diethylamine (0.26 ml), the mixture was stirred for 2 hours at room temperature. After the reaction, the solvent was removed by distillation under reduced pressure and the residue was dried under vacuum to obtain the ti...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
Primary amine
c1ccc2c(c1)Cc1ccccc12
null
c1ccccc1
HO-
CN(C)C=O
null
2
O=C(NCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)OCc1ccccc1>CN(C)C=O>N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-67abb265325d4c0db000f071744365b3
CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)cc1)Cc1ccccn1>>O=C(Cc1ccc(CNCc2ccccn2)cc1)N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(C=C1)CC(=O)N[C@H](C(=O)O)CCCNC1CCCC=2C=CC=NC12.Cl.O1CCOCC1>>Cl.N1=C(C=CC=C1)CNCC1=CC=C(C=C1)CC(=O)N[C@H](C(=O)O)CCCNC1CCCC=2C=CC=NC12
CC(C)(C)OC(=O)[N:10]([CH2:9][c:8]1[cH:7][cH:6][c:5]([CH2:4][C:3](=[O:2])[NH:20][C@@H:21]([CH2:22][CH2:23][CH2:24][NH:25][CH:26]2[CH2:27][CH2:28][CH2:29][c:30]3[cH:31][cH:32][cH:33][n:34][c:35]32)[C:36](=[O:37])[OH:38])[cH:19][cH:18]1)[CH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][n:17]1>>[O:2]=[C:3]([CH2:4][c:5]1[cH:6][cH...
CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)cc1)Cc1ccccn1
O=C(Cc1ccc(CNCc2ccccn2)cc1)N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O
null
null
CO
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(Cc1ccc(CNCc2ccccn2)cc1)NCCCCNC1CCCc2cccnc21
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[c:3]:[#7;a:4])-[C:5]-[c:6]>>[#7;a:4]:[c:3]-[C:2]-[NH;D2;+0:1]-[C:5]-[c:6]
null
[]
null
null
1.5
HOUR
The compound obtained in Example 8-8 (18.0 mg) was dissolved in methanol (0.2 ml) and 4 mol/l hydrochloric acid/dioxane solution was added. The mixture was stirred for 1.5 hours at room temperature. After the reaction, the solvent was removed by distillation. The residue was purified by silica gel column chromatography...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccccc1.c1ccncc1.c1cnc2c(c1)CCCC2
HO-
CO
null
1.5
CC(C)(C)OC(=O)N(Cc1ccc(CC(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)cc1)Cc1ccccn1>CO>O=C(Cc1ccc(CNCc2ccccn2)cc1)N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3ccd70d7c63d4afe90a7dd07edba6d48
O=C(O)c1ccc(CCBr)cc1>>COC(=O)c1ccc(CCBr)cc1
BrCCC1=CC=C(C(=O)O)C=C1.CCN=C=NCCCN(C)C.Cl.C=1C=CC2=C(C1)N=NN2O>>BrCCC1=CC=C(C(=O)OC)C=C1
[OH:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH2:9][CH2:10][Br:11])[cH:12][cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH2:9][CH2:10][Br:11])[cH:12][cH:13]1
O=C(O)c1ccc(CCBr)cc1
COC(=O)c1ccc(CCBr)cc1
null
null
CO
Miscellaneous
Protection of carboxylic acid
56520e0abb4535dce9a663824ca803b71c2c0dd72dfd246317d953596a987bd2
2ccc7a30191c2c171b49e8a0217bee87430687dd0f567141eca025a75b7e3136
c1ccccc1
[O;D1;H0:1]=[C:2](-[OH;D1;+0:3])-[c:4]>>[C;D1;H3:5]-[O;H0;D2;+0:3]-[C:2](=[O;D1;H0:1])-[c:4]
78.3
[{"value": 78.3, "product": "BrCCC1=CC=C(C(=O)OC)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
24
HOUR
Commercially available 4-bromoethylbenzoic acid (997.9 mg) was dissolved in methanol (30 ml). After the addition of WSCI hydrochloride (1.2527 g) and HOBt (598.5 mg), the solution was stirred for 24 hours at 60° C. After the reaction, the solvent was removed by distillation. The residue was dissolved in chloroform, was...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Ester
null
null
c1ccccc1
Other
CO
60
24
O=C(O)c1ccc(CCBr)cc1>CO>COC(=O)c1ccc(CCBr)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a78758e5b0fc4b538301b9f611812224
COC(=O)c1ccc(CCBr)cc1.NCc1ccccn1>>COC(=O)c1ccc(CCNCc2ccccn2)cc1
N1=C(C=CC=C1)CN.C(C)(C)N(CC)C(C)C.BrCCC1=CC=C(C(=O)OC)C=C1>>N1=C(C=CC=C1)CNCCC1=CC=C(C(=O)OC)C=C1
Br[CH2:10][CH2:9][c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:20][cH:19]1.[NH2:11][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][n:18]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH2:9][CH2:10][NH:11][CH2:12][c:13]2[cH:14][cH:15][cH:16][cH:17][n:18]2)[cH:19][cH:20]1
COC(=O)c1ccc(CCBr)cc1.NCc1ccccn1
COC(=O)c1ccc(CCNCc2ccccn2)cc1
null
null
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CCNCc2ccccn2)cc1
Br-[CH2;D2;+0:1]-[C:2]-[c:3].[#7;a:4]:[c:5]-[C:6]-[NH2;D1;+0:7]>>[#7;a:4]:[c:5]-[C:6]-[NH;D2;+0:7]-[CH2;D2;+0:1]-[C:2]-[c:3]
null
[]
80
CELSIUS
2
DAY
Commercially available 2-picolylamine (0.625 ml) was dissolved in toluene (15 ml) and diisopropylethylamine (0.715 ml) was added. After the addition of the compound obtained in Example 9-1 (499.7 mg), the mixture was stirred for two days at 80° C. After the reaction, toluene was added. The solution was washed with dist...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccncc1
HBr
C1(=CC=CC=C1)C
80
48
COC(=O)c1ccc(CCBr)cc1.NCc1ccccn1>C1(=CC=CC=C1)C>COC(=O)c1ccc(CCNCc2ccccn2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1c9322052b654c65b143e6b66ad1272d
COC(=O)c1ccc(CCN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>>CC(C)(C)OC(=O)N(CCc1ccc(C(=O)O)cc1)Cc1ccccn1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CCC1=CC=C(C(=O)OC)C=C1.CO.[OH-].[Na+]>>C(=O)(OC(C)(C)C)N(CCC1=CC=C(C(=O)O)C=C1)CC1=NC=CC=C1
C[O:17][C:15]([c:14]1[cH:13][cH:12][c:11]([CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:20][c:21]2[cH:22][cH:23][cH:24][cH:25][n:26]2)[cH:19][cH:18]1)=[O:16]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[OH:17])[cH:18][cH:1...
COC(=O)c1ccc(CCN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1
CC(C)(C)OC(=O)N(CCc1ccc(C(=O)O)cc1)Cc1ccccn1
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(CCNCc2ccccn2)cc1
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]
100.7
[{"value": 100.7, "product": "C(=O)(OC(C)(C)C)N(CCC1=CC=C(C(=O)O)C=C1)CC1=NC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
The compound obtained in Example 9-3 (446.1 mg) was dissolved in THF (4.5 ml) and methanol (4.5 ml) After the addition of 1 mol/l aqueous solution of sodium hydroxide (4.5 ml), the mixture was stirred for 5 hours at room temperature. After the reaction, the solvent was removed by distillation and the residue was dissol...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccncc1
Other
C1CCOC1
null
5
COC(=O)c1ccc(CCN(Cc2ccccn2)C(=O)OC(C)(C)C)cc1>C1CCOC1>CC(C)(C)OC(=O)N(CCc1ccc(C(=O)O)cc1)Cc1ccccn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f60a1a72dfff4c97885528a0b47a17df
CC(C)(C)OC(=O)N(CCc1ccc(C(=O)N[C@@H](CCCNCc2ccccn2)C(=O)O)cc1)Cc1ccccn1>>O=C(N[C@@H](CCCNCc1ccccn1)C(=O)O)c1ccc(CCNCc2ccccn2)cc1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CCC1=CC=C(C(=O)N[C@H](C(=O)O)CCCNCC2=NC=CC=C2)C=C1.Cl.O1CCOCC1>>Cl.N1=C(C=CC=C1)CNCCC1=CC=C(C(=O)N[C@H](C(=O)O)CCCNCC2=NC=CC=C2)C=C1
CC(C)(C)OC(=O)[N:26]([CH2:25][CH2:24][c:23]1[cH:22][cH:21][c:20]([C:3](=[O:2])[NH:4][C@@H:5]([CH2:6][CH2:7][CH2:8][NH:9][CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][n:16]2)[C:17](=[O:18])[OH:19])[cH:35][cH:34]1)[CH2:27][c:28]1[cH:29][cH:30][cH:31][cH:32][n:33]1>>[O:2]=[C:3]([NH:4][C@@H:5]([CH2:6][CH2:7][CH2:8][NH:9][CH2...
CC(C)(C)OC(=O)N(CCc1ccc(C(=O)N[C@@H](CCCNCc2ccccn2)C(=O)O)cc1)Cc1ccccn1
O=C(N[C@@H](CCCNCc1ccccn1)C(=O)O)c1ccc(CCNCc2ccccn2)cc1
null
null
CO
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(NCCCCNCc1ccccn1)c1ccc(CCNCc2ccccn2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]-[C:4]-[NH;D2;+0:1]-[C:2]-[C:3]
null
[]
null
null
75
MINUTE
The compound obtained in Example 10-1 (13.9 mg) was dissolved in methanol (0.28 ml) and 4 mol/l hydrochloric acid/dioxane solution (0.28 ml) was added to the solution. The mixture was stirred for 75 minutes at room temperature. After the completion of the reaction, the solvent was removed by distillation. The residue w...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccncc1.c1ccccc1.c1ccncc1
HO-
CO
null
1.25
CC(C)(C)OC(=O)N(CCc1ccc(C(=O)N[C@@H](CCCNCc2ccccn2)C(=O)O)cc1)Cc1ccccn1>CO>O=C(N[C@@H](CCCNCc1ccccn1)C(=O)O)c1ccc(CCNCc2ccccn2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f9b2fbe11f024165adc3b05c701f2695
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)o1>>O=C(N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O)c1ccc(CNCc2ccccn2)o1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=CC=C(O1)C(=O)N[C@H](C(=O)O)CCCNC1CCCC=2C=CC=NC12.Cl.O1CCOCC1>>Cl.N1=C(C=CC=C1)CNCC1=CC=C(O1)C(=O)N[C@H](C(=O)O)CCCNC1CCCC=2C=CC=NC12
CC(C)(C)OC(=O)[N:28]([CH2:27][c:26]1[cH:25][cH:24][c:23]([C:3](=[O:2])[NH:4][C@@H:5]([CH2:6][CH2:7][CH2:8][NH:9][CH:10]2[CH2:11][CH2:12][CH2:13][c:14]3[cH:15][cH:16][cH:17][n:18][c:19]32)[C:20](=[O:21])[OH:22])[o:36]1)[CH2:29][c:30]1[cH:31][cH:32][cH:33][cH:34][n:35]1>>[O:2]=[C:3]([NH:4][C@@H:5]([CH2:6][CH2:7][CH2:8][N...
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)o1
O=C(N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O)c1ccc(CNCc2ccccn2)o1
null
null
CO
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(NCCCCNC1CCCc2cccnc21)c1ccc(CNCc2ccccn2)o1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[c:3]:[#8;a:4])-[C:5]-[c:6]:[#7;a:7]>>[#7;a:7]:[c:6]-[C:5]-[NH;D2;+0:1]-[C:2]-[c:3]:[#8;a:4]
null
[]
null
null
3
HOUR
The compound obtained in Example 11-5 (30.6 mg) was dissolved in methanol (0.7 ml), and 4 mol/l hydrochloric acid/dioxane solution (0.7 ml) was added. The mixture was stirred for 3 hours at room temperature. After the reaction, the solvent was removed by distillation. The residue was purified by silica gel column chrom...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1cnc2c(c1)CCCC2.c1ccoc1.c1ccncc1
HO-
CO
null
3
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC2CCCc3cccnc32)C(=O)O)o1>CO>O=C(N[C@@H](CCCNC1CCCc2cccnc21)C(=O)O)c1ccc(CNCc2ccccn2)o1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d50513840ecb42d3af2d9a84c664dac4
COC(=O)c1ccc(C)nc1.NCc1ccccn1>>COC(=O)c1ccc(CNCc2ccccn2)nc1
CC1=NC=C(C(=O)OC)C=C1.BrN1C(CCC1=O)=O.C([O-])([O-])=O.[K+].[K+].N1=C(C=CC=C1)CN>>N1=C(C=CC=C1)CNCC1=NC=C(C(=O)OC)C=C1
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH3:9])[n:18][cH:19]1.[NH2:10][CH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][n:17]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH2:9][NH:10][CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][n:17]2)[n:18][cH:19]1
COC(=O)c1ccc(C)nc1.NCc1ccccn1
COC(=O)c1ccc(CNCc2ccccn2)nc1
null
null
C(Cl)(Cl)Cl.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
3c2788b3f372b76c1d2ee0d77963cb247b210aa8a28e76637b4e731826c4252a
c6874c6af41d3b1c4f7668e1cd342c90252d0e77f4317d31b3193ebc2f9501a3
c1ccc(CNCc2ccccn2)nc1
[#7;a:1]:[c:2]-[C:3]-[NH2;D1;+0:4].[CH3;D1;+0:5]-[c:6](:[c:7]):[#7;a:8]:[c:9]>>[#7;a:1]:[c:2]-[C:3]-[NH;D2;+0:4]-[CH2;D2;+0:5]-[c:6](:[c:7]):[#7;a:8]:[c:9]
null
[]
70
CELSIUS
22
HOUR
Commercially available methyl 6-methylnicotinate (2.5116 g) was dissolved in chloroform (50 ml), and N-bromosuccinimide (3.5682 g) and azoisobutylonitrile (290.4 mg) were added to the solution. The mixture was stirred for 22 hours at 70° C. After the reaction, the solvent was removed by distillation. The residue was pu...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Secondary amine
null
null
c1ccncc1.c1ccncc1
null
C(Cl)(Cl)Cl.CN(C)C=O
70
22
COC(=O)c1ccc(C)nc1.NCc1ccccn1>C(Cl)(Cl)Cl.CN(C)C=O>COC(=O)c1ccc(CNCc2ccccn2)nc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a78d72c6fe744272bcfd3a458c7ab371
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)nc1>>CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C(=O)OC)C=C1.[OH-].[Na+]>>C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C(=O)O)C=C1
C[O:23][C:21]([c:20]1[cH:19][cH:18][c:17]([CH2:16][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][n:15]2)[n:25][cH:24]1)=[O:22]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][n:15]1)[CH2:16][c:17]1[cH:18][cH:19][c:20]([...
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)nc1
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(CNCc2ccccn2)nc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
82.3
[{"value": 82.3, "product": "C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C(=O)O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
The compound obtained in Example 12-2 (351.3 mg) was dissolved in methanol (3.5 ml) and THF (3.5 ml). After the addition of 1 mol/l aqueous solution of sodium hydroxide (3.5 ml), the mixture was stirred for 2 hours at room temperature. After the reaction, the solvent was removed by distillation. The residue was dissolv...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccncc1.c1ccncc1
Other
CO.C1CCOC1
null
2
COC(=O)c1ccc(CN(Cc2ccccn2)C(=O)OC(C)(C)C)nc1>CO.C1CCOC1>CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5d6d23489ab9488382c98bbf6eb9445a
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1.N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O>>CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC(=O)OCc2ccccc2)C(=O)O)cn1
C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C(=O)O)C=C1.CCN=C=NCCCN(C)C.Cl.C=1C=CC2=C(C1)N=NN2O.C(=O)(OCC1=CC=CC=C1)NCCC[C@H](N)C(=O)O>>C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C=C1)C(=O)N[C@@H](CCCNC(=O)OCC1=CC=CC=C1)C(=O)O
O[C:21]([c:20]1[cH:19][cH:18][c:17]([CH2:16][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][n:15]2)[n:43][cH:42]1)=[O:22].[NH2:23][C@@H:24]([CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:30])[O:31][CH2:32][c:33]1[cH:34][cH:35][cH:36][cH:37][cH:38]1)[C:39](=[O:40])[OH:41]>>[C...
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1.N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC(=O)OCc2ccccc2)C(=O)O)cn1
null
null
CN(C)C=O
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCCCNC(=O)c1ccc(CNCc2ccccn2)nc1)OCc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7].[C:8]-[C:9](-[NH2;D1;+0:10])-[C:11](=[O;D1;H0:12])-[O;D1;H1:13]>>[C:8]-[C:9](-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7])-[C:11](=[O;D1;H0:12])-[O;D1;H1:13]
107.6
[{"value": 107.6, "product": "C(=O)(OC(C)(C)C)N(CC1=NC=CC=C1)CC1=NC=C(C=C1)C(=O)N[C@@H](CCCNC(=O)OCC1=CC=CC=C1)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
The compound obtained in Example 8-6 (165.3 mg) was dissolved in DMF (3 ml). After the addition of WSCI hydrochloride (78.5 mg), HOBt (40.1 mg), and the compound obtained in Example 12-3 (90.4 mg), the mixture was stirred for 23 hours at room temperature. After the reaction, the solvent was removed by distillation. The...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccncc1.c1ccncc1.c1ccccc1
HO-
CN(C)C=O
null
null
CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)O)cn1.N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O>CN(C)C=O>CC(C)(C)OC(=O)N(Cc1ccccn1)Cc1ccc(C(=O)N[C@@H](CCCNC(=O)OCc2ccccc2)C(=O)O)cn1