dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6d8bca8ea5284e3f8ed438df0067ff81
Cn1ccnc1.O=C(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1>>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1
Cl[Si](CC)(CC)CC.ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)F.[Li]CCCC.CCCCCC.[Li]CCCC.CCCCCC.CN1C=NC=C1>>ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F
[CH3:1][n:2]1[cH:3][n:4][cH:5][cH:6]1.[C:7](=[O:8])([c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1)[c:16]1[cH:17][cH:18][c:19]2[n:20][c:21]([Cl:22])[n:23][c:24](-[c:25]3[cH:26][cH:27][cH:28][c:29]([Cl:30])[cH:31]3)[c:32]2[cH:33]1>>[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][cH:11][c:12]([F:13])[c...
Cn1ccnc1.O=C(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1
null
null
O.CCOC(=O)C.C1CCOC1
C-C Coupling
OtherReaction
3433c90914e9b30e9a7c8b7d908911f5bba34cfc8cc88706413738357bc5fa4d
454f67ba8644982dc9f605915a0f36178771eadaffb50d3f1e0f17f2b6fdeb10
c1ccc(-c2ncnc3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[cH;D2;+0:6]:1.[O;H0;D1;+0:7]=[C;H0;D3;+0:8](-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]>>[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[c;H0;D3;+0:6]:1-[C;H0;D4;+0:8](-[OH;D1;+0:7])(-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]
0.8
[{"value": 0.8, "product": "ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-70
CELSIUS
15
MINUTE
BuLi 1.6M in hexane (46.5 ml, 0.0744 mol) was added dropwise at −70° C. to a mixture of 1-methyl-1H-imidazole (0.0744 mol) in THF (70 ml) under N2 flow. Chlorotriethyl-silane (0.0765 mol) was added dropwise at −70° C. The mixture was stirred at −70° C. for 15 minutes. BuLi 1.6M in hexane (41 ml, 0.0659 mol) was added d...
10.6084/m9.figshare.5104873.v1
null
Ketone
Tertiary alcohol
c1c[nH]cn1
c1cnc[nH]1
c1cnc[nH]1.c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
null
O.CCOC(=O)C.C1CCOC1
-70
0.25
Cn1ccnc1.O=C(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1>O.CCOC(=O)C.C1CCOC1>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eecfee5fb078407e937e0238498d097c
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1.[N-]=[N+]=[N-]>>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12
ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F.[N-]=[N+]=[N-].[Na+]>>ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2
Cl[c:31]1[n:30][c:22](-[c:23]2[cH:24][cH:25][cH:26][c:27]([Cl:28])[cH:29]2)[c:20]2[c:19]([cH:18][cH:17][c:16]([C:7]([c:6]3[n:2]([CH3:1])[cH:3][n:4][cH:5]3)([OH:8])[c:9]3[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]3)[cH:21]2)[n:35]1.[N-:32]=[N+:34]=[N-:33]>>[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][c...
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1.[N-]=[N+]=[N-]
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12
null
null
CN(C)C=O
Aromatic Heterocycle Formation
OtherReaction
4e0cb3e54897e660c5677e719a9c21ad2978ab17efb16dd9052e527979ac46a1
155f764f095c8454a4ad08aaa42f1abcb15d5bc1d4f122e4bcc624dd834362f2
c1ccc(-c2nc3nnnn3c3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5](:[c:6]):[n;H0;D2;+0:7]:1.[N-;H0;D1:8]=[N+;H0;D2:9]=[N-;H0;D1:10]>>[c:6]:[c:5]1:[c:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]2:[n;H0;D2;+0:8]:[n;H0;D2;+0:10]:[n;H0;D2;+0:9]:[n;H0;D3;+0:7]:1:2
58
[{"value": 58.0, "product": "ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.6, "product": "ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
2
HOUR
A mixture of intermediate 7 (0.0125 mol) and sodium azide (0.038 mol) in DMF (60 ml) was stirred at 90° C. for 2 hours, then brought to room temperature, poured out into ice water and stirred. The precipitate was filtered, washed with water, taken up in DCM, filtered, washed with diethyl ether and dried under a vacuo, ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncncc2c1
c1ccc2c(c1)cnc1nnnn12
c1cnc[nH]1.c1ccccc1.c1ccccc1.c1ccc2c(c1)cnc1nnnn12
Other
CN(C)C=O
90
2
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2nc(Cl)nc(-c3cccc(Cl)c3)c2c1.[N-]=[N+]=[N-]>CN(C)C=O>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-97c34b6fceb2400cb6294c78a72f8bf3
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12>>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2
C(Cl)Cl.[B-].[Na+].ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2>>ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2
[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1)[c:16]1[cH:17][cH:18][c:19]2[c:20]([cH:21]1)[c:22](-[c:23]1[cH:24][cH:25][cH:26][c:27]([Cl:28])[cH:29]1)[n:30][c:31]1[n:32][n:33][n:34][n:35]21>>[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][cH:11][c:12...
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2
null
null
CO
Reduction
OtherReaction
68fa0e5ecb7fd022bbef2c0545f4aab67cdefa951d7696965b374d746a3ba330
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc(C2Nc3nnnn3-c3ccc(C(c4ccccc4)c4cnc[nH]4)cc32)cc1
[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5]):[c;H0;D3;+0:6](-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10]:[c:11]):[n;H0;D2;+0:12]:[c:13]2:[#7;a:14]:[#7;a:15]:[#7;a:16]:[n;H0;D3;+0:17]:2:1>>[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[CH;D3;+0:6](-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10]:[c:11])-[NH;D2;+0:12]-[c:13]2:[#7;a:14]:[#7;a:15]:[...
21.5
[{"value": 21.0, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 21.5, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Sodium hydroborate (0.001 mol) was added portionwise at room temperature to a mixture of intermediate 8 (0.001 mol) in methanol (5 ml). The mixture was stirred at room temperature for 2 hours and poured out into ice water. DCM was added. The organic layer was washed with water, separated, dried (MgSO4), filtered and th...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2c(c1)cnc1nnnn12
c1ccc2c(c1)CNc1nnnn12
c1cnc[nH]1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CNc1nnnn12
null
CO
null
2
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)nc1nnnn12>CO>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7bfe84fd85094276ad6be475386f2c07
COc1ccc(C(=O)N(C)OC)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1>>COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
[Li]CCCC.BrC=1C=CC=2C(=C(ON2)C2=CC(=CC=C2)Cl)C1.CON(C(C1=CC=C(C=C1)OC)=O)C>>ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)OC
CON(C)[C:7]([c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:26][cH:25]1)=[O:8].Br[c:9]1[cH:10][cH:11][c:12]2[n:13][o:14][c:15](-[c:16]3[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]3)[c:23]2[cH:24]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[n:13][o:14][c:15](-[c:16]4[cH:17][cH:18][cH:19][c:20]...
COc1ccc(C(=O)N(C)OC)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1
COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
null
null
C1CCOC1
C-C Coupling
OtherReaction
ed7d0f62acc084fc2d1c32686cb3eb636bc801b108aa5e5891b600d5eadc5405
7d9aa59f8ecc532475d910f9ab122332ecbb7f9444a37371b7c1bac80798d342
O=C(c1ccccc1)c1ccc2noc(-c3ccccc3)c2c1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[#7;a:5]:[#8;a:6]:[c:7]:[c:8]:2:[c:9]:1.C-O-N(-C)-[C;H0;D3;+0:10](=[O;D1;H0:11])-[c:12](:[c:13]):[c:14]>>[O;D1;H0:11]=[C;H0;D3;+0:10](-[c:12](:[c:13]):[c:14])-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[#7;a:5]:[#8;a:6]:[c:7]:[c:8]:2:[c:9]:1
41
[{"value": 41.0, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)OC", "details": "PERCENTYIELD", "is_desired": false}]
-70
CELSIUS
10
MINUTE
5-bromo-3-(3-chlorophenyl)-2,1-benzisoxazole (0.13 m) was added at −70° C. to THF (300 ml) under N2 flow. A solution of BuLi (0.143 mol) was added dropwise. The mixture was stirred at −70° C. for 10 minutes. A solution of N,4-dimethoxy-N-methylbenzamide (0.117 mol) in THF (100 ml) was added dropwise at −70° C. The mixt...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amide
Ketone
c1ccc2nocc2c1
c1ccc2nocc2c1
c1ccccc1.c1ccc2nocc2c1.c1ccccc1
HBr
C1CCOC1
-70
0.166667
COc1ccc(C(=O)N(C)OC)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1>C1CCOC1>COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-caaed9f827414c17971404255f2117a8
COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>>COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)OC.C1CCOC1>>NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(=O)C1=CC(=CC=C1)Cl
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[n:13][o:16][c:15](-[c:17]4[cH:18][cH:19][cH:20][c:21]([Cl:22])[cH:23]4)[c:14]3[cH:24]2)[cH:25][cH:26]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]([NH2:13])[c:14]([C:15](=[O:16])[c:17]3[cH:18][cH:19][cH:20][c:2...
COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
null
null
O
Miscellaneous
OtherReaction
63dfc430e67d3a7ada3c7e8f6e094ee16a92b905651085a196381d3119990ee1
2e99338cc955e46b2c0e811178d7128dca9a68ef9fbb467724eba7220efe12b0
O=C(c1ccccc1)c1cccc(C(=O)c2ccccc2)c1
[c:1]:[c:2]1:[n;H0;D2;+0:3]:[o;H0;D2;+0:4]:[c;H0;D3;+0:5](-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:11]:1:[c:12]>>[NH2;D1;+0:3]-[c:2](:[c:1]):[c:11](-[C;H0;D3;+0:5](=[O;H0;D1;+0:4])-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:12]
104.6
[{"value": 104.6, "product": "NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(=O)C1=CC(=CC=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Intermediate 10 (0.0536 mol) was added at room temperature to THF (200 ml). TiCl3 15% in water (120 ml) was added dropwise at room temperature. The mixture was stirred at room temperature for 3 hours, poured out into ice water and extracted with DCM. The organic layer was separated, washed with K2CO3 10% then with wate...
10.6084/m9.figshare.5104873.v1
null
null
Ketone.Primary amine
c1ccc2nocc2c1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccccc1
null
O
null
3
COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>O>COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cc951cb177d4449cbb7983bb42eb8ee5
COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl>>COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
ClC(C(=O)Cl)(Cl)Cl.NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(=O)C1=CC(=CC=C1)Cl.C(C)N(CC)CC>>ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]([NH2:13])[c:20]([C:21](=[O:22])[c:23]3[cH:24][cH:25][cH:26][c:27]([Cl:28])[cH:29]3)[cH:30]2)[cH:31][cH:32]1.Cl[C:14](=[O:15])[C:16]([Cl:17])([Cl:18])[Cl:19]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]([NH:13][C:...
COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl
COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
null
null
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(c1ccccc1)c1cccc(C(=O)c2ccccc2)c1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[Cl;D1;H0:4])(-[Cl;D1;H0:5])-[Cl;D1;H0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]=[O;D1;H0:12]>>[Cl;D1;H0:4]-[C:3](-[Cl;D1;H0:5])(-[Cl;D1;H0:6])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]=[O;D1;H0:12]
100
[{"value": 100.0, "product": "ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
5
CELSIUS
30
MINUTE
A mixture of intermediate 11 (0.0536 mol) in DCM (200 ml) was cooled to 5° C. under N2 flow. A solution of trichloro-acetylchloride (0.0643 mol) was added dropwise at 5° C. The mixture was stirred at 5° C. for 30 minutes. A solution of triethylamine (0.0643 mol) was added dropwise at 5° C. The mixture was stirred at 5°...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
5
0.5
COc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl>C(Cl)Cl>COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0577cb35c37947539e65a4f808a902ca
COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]>>COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
[NH4+].C(C)(=O)[O-].ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)OC)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl>>ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)OC)=O)=O
O=[C:17]([c:18]1[cH:19][cH:20][cH:21][c:22]([Cl:23])[cH:24]1)[c:25]1[c:12]([NH:13][C:14](C(Cl)(Cl)Cl)=[O:15])[cH:11][cH:10][c:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:28][cH:27]2)=[O:8])[cH:26]1.[NH4+:16]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[nH:13][c:14](=[O:15])[n:16][...
COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]
COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
null
null
CS(=O)C
Aromatic Heterocycle Formation
OtherReaction
34356251393ced07649e3f2d79584418a4a8dc983e24c794ec9fd18e790ecc31
1620ff2b4fcf2514dc5381b8c0e77d605f9d7258e5a6b5dfb277498e8a5ebb1a
O=C(c1ccccc1)c1ccc2[nH]c(=O)nc(-c3ccccc3)c2c1
Cl-C(-Cl)(-Cl)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:3]-[c:4](:[c:5]):[c:6](-[C;H0;D3;+0:7](=O)-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]):[c:13].[NH4+;D0:14]>>[O;D1;H0:2]=[c;H0;D3;+0:1]1:[n;H0;D2;+0:14]:[c;H0;D3;+0:7](-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]):[c:6](:[c:13]):[c:4](:[c:5]):[nH;D2;+0:3]:1
77.3
[{"value": 77.0, "product": "ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)OC)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.3, "product": "ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)OC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
4
HOUR
Acetic acid, ammonium salt (0.107 mol) was added at room temperature to a mixture of intermediate 12 (0.0536 mol) in DMSO (250 ml). The mixture was stirred at 60° C. for 4 hours then brought to room temperature, poured out into ice water and stirred. The precipitate was filtered, washed with water and taken up in warm ...
10.6084/m9.figshare.5104873.v1
null
Trichloro group.Ketone.Secondary amide
null
c1ccccc1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
HCl
CS(=O)C
60
4
COc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]>CS(=O)C>COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e9c107f6ada94c5c89435144078d6159
COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl>>COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)OC)=O)=O.P(=O)(Cl)(Cl)Cl>>ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)OC
O=[c:14]1[nH:13][c:12]2[cH:11][cH:10][c:9]([C:7]([c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:28][cH:27]3)=[O:8])[cH:26][c:25]2[c:17](-[c:18]2[cH:19][cH:20][cH:21][c:22]([Cl:23])[cH:24]2)[n:16]1.O=P(Cl)(Cl)[Cl:15]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[n:13][c:14]([Cl:15])[n:16][c:17]...
COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl
COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
O=C(c1ccccc1)c1ccc2ncnc(-c3ccccc3)c2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](:[c:7]):[nH;D2;+0:8]:1>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](:[c:7]):[n;H0;D2;+0:8]:1
87
[{"value": 87.0, "product": "ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)OC", "details": "PERCENTYIELD", "is_desired": false}]
100
CELSIUS
3
HOUR
Intermediate 13 (0.0432 mol) was added at room temperature to phosphoryl chloride (150 ml). The mixture was stirred at 100° C. for 3 hours then brought to room temperature. The solvent was evaporated till dryness. The residue was taken up in DCM. The solvent was evaporated. The residue was taken up in DCM. The mixture ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
HCl
null
100
3
COc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl>>COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4a4fac1bba674e4796294de9779081be
COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1>>COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
[Li]CCCC.CN1C=NC=C1.ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)OC.Cl[Si](CC)(CC)CC>>ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[n:13][c:14]([Cl:15])[n:16][c:17](-[c:18]4[cH:19][cH:20][cH:21][c:22]([Cl:23])[cH:24]4)[c:25]3[cH:26]2)[cH:33][cH:34]1.[cH:27]1[cH:28][n:29][cH:30][n:31]1[CH3:32]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH:10][cH:11][c:12]3[n:...
COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1
COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
null
null
O.CCOC(=O)C.C1CCOC1
C-C Coupling
OtherReaction
05395e7d28d1a7c287cdf9872044b38b254b469c1c451b45b37d37651dd6bc83
454f67ba8644982dc9f605915a0f36178771eadaffb50d3f1e0f17f2b6fdeb10
c1ccc(-c2ncnc3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[cH;D2;+0:6]:1.[O;H0;D1;+0:7]=[C;H0;D3;+0:8](-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]>>[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[c;H0;D3;+0:6]:1-[C;H0;D4;+0:8](-[OH;D1;+0:7])(-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]
59
[{"value": 59.0, "product": "ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.9, "product": "ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
nBuLi (0.0665 mol) was added dropwise at −70° C. to a solution of 1-methyl-1H-imidazole (0.0665 mol) in THF (60 ml) under N2 flow. The mixture was stirred for 15 minutes. Chlorotriethyl-silane (0.0684 mol) was added dropwise. The mixture was stirred for 15 minutes. nBuli (0.059 mol) was added dropwise. The mixture was ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Tertiary alcohol
c1c[nH]cn1
c1c[nH]cn1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1.c1c[nH]cn1
null
O.CCOC(=O)C.C1CCOC1
null
0.25
COc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1>O.CCOC(=O)C.C1CCOC1>COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3174410cc7aa4d319705df78235927e0
COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]>>COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC.[N-]=[N+]=[N-].[Na+]>>ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2
Cl[c:24]1[n:23][c:15](-[c:16]2[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]2)[c:13]2[c:12]([cH:11][cH:10][c:9]([C:7]([c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:36][cH:35]3)([OH:8])[c:29]3[cH:30][n:31][cH:32][n:33]3[CH3:34])[cH:14]2)[n:28]1.[N-:25]=[N+:27]=[N-:26]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH...
COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]
COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
null
null
CN(C)C=O
Aromatic Heterocycle Formation
OtherReaction
4e0cb3e54897e660c5677e719a9c21ad2978ab17efb16dd9052e527979ac46a1
155f764f095c8454a4ad08aaa42f1abcb15d5bc1d4f122e4bcc624dd834362f2
c1ccc(-c2nc3nnnn3c3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5](:[c:6]):[n;H0;D2;+0:7]:1.[N-;H0;D1:8]=[N+;H0;D2:9]=[N-;H0;D1:10]>>[c:6]:[c:5]1:[c:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]2:[n;H0;D2;+0:8]:[n;H0;D2;+0:10]:[n;H0;D2;+0:9]:[n;H0;D3;+0:7]:1:2
80.7
[{"value": 80.0, "product": "ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.7, "product": "ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
2
HOUR
A mixture of intermediate 15 (0.0224 mol) and sodium azide (0.067 mol) in DMF (120 ml) was stirred at 90° C. for 2 hours, brought to room temperature, poured out into ice water and stirred. The precipitate was filtered, washed with water and taken up in DCM. The organic layer was washed with water, separated, dried (Mg...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncncc2c1
c1ccc2c(c1)cnc1nnnn12
c1ccccc1.c1ccccc1.c1ccc2c(c1)cnc1nnnn12.c1c[nH]cn1
Other
CN(C)C=O
90
2
COc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]>CN(C)C=O>COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4dfd5f10146d40e5832362af6c04be9c
COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1>>COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
C(Cl)Cl.[BH4-].[Na+].ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2>>ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[c:15](-[c:16]2[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]2)[n:23][c:24]2[n:25][n:26][n:27][n:28]32)[c:29]2[cH:30][n:31][cH:32][n:33]2[CH3:34])[cH:35][cH:36]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH:10][cH:...
COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
null
null
CO
Reduction
OtherReaction
68fa0e5ecb7fd022bbef2c0545f4aab67cdefa951d7696965b374d746a3ba330
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc(C2Nc3nnnn3-c3ccc(C(c4ccccc4)c4cnc[nH]4)cc32)cc1
[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5]):[c;H0;D3;+0:6](-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10]:[c:11]):[n;H0;D2;+0:12]:[c:13]2:[#7;a:14]:[#7;a:15]:[#7;a:16]:[n;H0;D3;+0:17]:2:1>>[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[CH;D3;+0:6](-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10]:[c:11])-[NH;D2;+0:12]-[c:13]2:[#7;a:14]:[#7;a:15]:[...
67
[{"value": 67.0, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.7, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
NaBH4 (0.003 mol) was added portionwise at room temperature to a mixture of intermediate 16 (0.003 mol) in methanol (15 ml). The mixture was stirred at room temperature for 2 hours and poured out into ice water. DCM was added. The mixture was extracted with DCM. The organic layer was separated, dried (MgSO4), filtered,...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2c(c1)cnc1nnnn12
c1ccc2c(c1)CNc1nnnn12
c1ccccc1.c1ccccc1.c1ccc2c(c1)CNc1nnnn12.c1c[nH]cn1
null
CO
null
2
COc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1>CO>COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-da903ade3be946ffa0911b31ee60f241
Cc1ccc(C=O)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1>>Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
BrC=1C=CC=2C(=C(ON2)C2=CC(=CC=C2)Cl)C1.CC1=CC=C(C=O)C=C1.[Li]CCCC.CCCCCC>>ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(O)C2=CC=C(C=C2)C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH:6]=[O:7])[cH:24][cH:25]1.Br[c:8]1[cH:9][cH:10][c:11]2[n:12][o:13][c:14](-[c:15]3[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]3)[c:22]2[cH:23]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH:6]([OH:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][o:13][c:14](-[c:15]4[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]4)...
Cc1ccc(C=O)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1
Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
null
null
C1CCOC1
C-C Coupling
Grignard_alcohol
f822b053a4342903753b2398efb1ef26df143aa50697f50ef6a150fdf12a512a
1c0bd0afc1d5e370e3c8193faf738f03752295e40fa0eb99c756011e9a4be26b
c1ccc(Cc2ccc3noc(-c4ccccc4)c3c2)cc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]2:[c:4]:[#8;a:5]:[#7;a:6]:[c:7]:2:[c:8]:[c:9]:1.[O;H0;D1;+0:10]=[CH;D2;+0:11]-[c:12](:[c:13]):[c:14]>>[OH;D1;+0:10]-[CH;D3;+0:11](-[c:12](:[c:13]):[c:14])-[c;H0;D3;+0:1]1:[c:2]:[c:3]2:[c:4]:[#8;a:5]:[#7;a:6]:[c:7]:2:[c:8]:[c:9]:1
38.3
[{"value": 38.3, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(O)C2=CC=C(C=C2)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.3, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(O)C2=CC=C(C=C2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-70
CELSIUS
15
MINUTE
nBuLi 1.6 M in hexane (0.112 mol) was added dropwise at −70° C. under N2 flow to a mixture of 5-bromo-3-(3-chlorophenyl)-2,1-benzisoxazole (0.097 mol) in THF (300 ml). The mixture was stirred at −70° C. for 15 min. A mixture of 4-methylbenzaldehyde (0.112 mol) in THF (100 ml) was added dropwise. The mixture was stirred...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aldehyde
Secondary alcohol
c1ccc2nocc2c1
c1ccc2nocc2c1
c1ccccc1.c1ccc2nocc2c1.c1ccccc1
Br-
C1CCOC1
-70
0.25
Cc1ccc(C=O)cc1.Clc1cccc(-c2onc3ccc(Br)cc23)c1>C1CCOC1>Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b8c3594ec5a64ca4a578b8f45428384d
Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>>Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(O)C2=CC=C(C=C2)C>>ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH:6]([OH:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][o:13][c:14](-[c:15]4[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]4)[c:22]3[cH:23]2)[cH:24][cH:25]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][o:13][c:14](-[c:15]4[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]4)[c...
Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
null
O=[Mn]=O
O1CCOCC1
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
c7c20d2959ac48847b03cc1265962cf99a8ec8a85900c087dabb30077298c66c
767cfd93f5821ebb9e1e72addd9cb404b20b0c821d246ae6b87a5776b74a455b
O=C(c1ccccc1)c1ccc2noc(-c3ccccc3)c2c1
[OH;D1;+0:1]-[CH;D3;+0:2](-[c:3](:[c:4]):[c:5])-[c:6](:[c:7]):[c:8]>>[O;H0;D1;+0:1]=[C;H0;D3;+0:2](-[c:3](:[c:4]):[c:5])-[c:6](:[c:7]):[c:8]
100
[{"value": 100.0, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 100.0, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
2
HOUR
A mixture of intermediate 18 (0.071 mol) and MnO2 (0.287 mol) in 1,4-dioxane (250 ml) was stirred at 80° C. for 2 hours, then cooled to room temperature, filtered over celite and washed with DCM. The solvent was evaporated till dryness, yielding 24.7 g (100%) of [3-(3-chlorophenyl)-2,1-benzisoxazol-5-yl](4-methylphenyl...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
Ketone
null
null
c1ccccc1.c1ccc2nocc2c1.c1ccccc1
null
O=[Mn]=O.O1CCOCC1
80
2
Cc1ccc(C(O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>O=[Mn]=O.O1CCOCC1>Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-af8ca250e0d44d028c48e246ff3d4583
Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>>Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)C>>NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(=O)C1=CC(=CC=C1)Cl
[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][o:15][c:14](-[c:16]4[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]4)[c:13]3[cH:23]2)[cH:24][cH:25]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]([NH2:12])[c:13]([C:14](=[O:15])[c:16]3[cH:17][cH:18][cH:19][c:20]([Cl:21])[...
Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
null
null
O.C1CCOC1
Miscellaneous
OtherReaction
63dfc430e67d3a7ada3c7e8f6e094ee16a92b905651085a196381d3119990ee1
2e99338cc955e46b2c0e811178d7128dca9a68ef9fbb467724eba7220efe12b0
O=C(c1ccccc1)c1cccc(C(=O)c2ccccc2)c1
[c:1]:[c:2]1:[n;H0;D2;+0:3]:[o;H0;D2;+0:4]:[c;H0;D3;+0:5](-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:11]:1:[c:12]>>[NH2;D1;+0:3]-[c:2](:[c:1]):[c:11](-[C;H0;D3;+0:5](=[O;H0;D1;+0:4])-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]):[c:12]
82.6
[{"value": 82.6, "product": "NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(=O)C1=CC(=CC=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.5, "product": "NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(=O)C1=CC(=CC=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A mixture of intermediate 19 (0.071 mol) in THF (250 ml) was cooled on an ice bath. TiCl3 15% in water (250 ml) was added dropwise. The mixture was stirred at room temperature overnight, then poured out into ice water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was e...
10.6084/m9.figshare.5104873.v1
null
null
Ketone.Primary amine
c1ccc2nocc2c1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccccc1
null
O.C1CCOC1
null
8
Cc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1>O.C1CCOC1>Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2db6989bc5c143c3b9173ee3da57c93d
Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl>>Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
ClC(C(=O)Cl)(Cl)Cl.C(C)N(CC)CC.NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(=O)C1=CC(=CC=C1)Cl>>ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl
[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]([NH2:12])[c:19]([C:20](=[O:21])[c:22]3[cH:23][cH:24][cH:25][c:26]([Cl:27])[cH:28]3)[cH:29]2)[cH:30][cH:31]1.Cl[C:13](=[O:14])[C:15]([Cl:16])([Cl:17])[Cl:18]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]([NH:12][C:13](=[O:14])...
Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl
Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
null
null
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(c1ccccc1)c1cccc(C(=O)c2ccccc2)c1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[Cl;D1;H0:4])(-[Cl;D1;H0:5])-[Cl;D1;H0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]=[O;D1;H0:12]>>[Cl;D1;H0:4]-[C:3](-[Cl;D1;H0:5])(-[Cl;D1;H0:6])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]=[O;D1;H0:12]
99.8
[{"value": 99.8, "product": "ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Intermediate 20 (0.0085 mol) was added at 5° C. to DCM (30 ml) under N2 flow. trichloro-acetyl chloride (0.01 mol) then triethylamine (0.01 mol) were added dropwise. The mixture was brought to room temperature, stirred at room temperature for 3 hours, poured out into ice water and extracted with DCM. The organic layer ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
null
3
Cc1ccc(C(=O)c2ccc(N)c(C(=O)c3cccc(Cl)c3)c2)cc1.O=C(Cl)C(Cl)(Cl)Cl>C(Cl)Cl>Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ef68f45e67c84ed5b740f889c172e6d1
Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]>>Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
ClC(C(=O)NC1=C(C=C(C=C1)C(C1=CC=C(C=C1)C)=O)C(C1=CC(=CC=C1)Cl)=O)(Cl)Cl.[NH4+].C(C)(=O)[O-]>>ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)C)=O)=O
O=[C:16]([c:17]1[cH:18][cH:19][cH:20][c:21]([Cl:22])[cH:23]1)[c:24]1[c:11]([NH:12][C:13](C(Cl)(Cl)Cl)=[O:14])[cH:10][cH:9][c:8]([C:6]([c:5]2[cH:4][cH:3][c:2]([CH3:1])[cH:27][cH:26]2)=[O:7])[cH:25]1.[NH4+:15]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]3[nH:12][c:13](=[O:14])[n:15][c:16](-[c:17...
Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]
Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
null
null
CS(=O)C
Aromatic Heterocycle Formation
OtherReaction
34356251393ced07649e3f2d79584418a4a8dc983e24c794ec9fd18e790ecc31
1620ff2b4fcf2514dc5381b8c0e77d605f9d7258e5a6b5dfb277498e8a5ebb1a
O=C(c1ccccc1)c1ccc2[nH]c(=O)nc(-c3ccccc3)c2c1
Cl-C(-Cl)(-Cl)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:3]-[c:4](:[c:5]):[c:6](-[C;H0;D3;+0:7](=O)-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]):[c:13].[NH4+;D0:14]>>[O;D1;H0:2]=[c;H0;D3;+0:1]1:[n;H0;D2;+0:14]:[c;H0;D3;+0:7](-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]):[c:6](:[c:13]):[c:4](:[c:5]):[nH;D2;+0:3]:1
63.4
[{"value": 63.0, "product": "ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.4, "product": "ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
4
HOUR
A mixture of intermediate 21 (0.0085 mol) and acetic acid, ammonium salt (0.0169 mol) in DMSO (42 ml) was stirred at 60° C. for 4 hours then cooled and poured out into ice water. The precipitate was filtered, washed with water, taken up in warm CH3CN, filtered off and dried under a vacuo, yielding 2.02 g (63%) of 4-(3-...
10.6084/m9.figshare.5104873.v1
null
Trichloro group.Ketone.Secondary amide
null
c1ccccc1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
HCl
CS(=O)C
60
4
Cc1ccc(C(=O)c2ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c3cccc(Cl)c3)c2)cc1.[NH4+]>CS(=O)C>Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bd8f502824d94ebf940f9a1a526c49ba
Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl>>Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
ClC=1C=C(C=CC1)C1=NC(NC2=CC=C(C=C12)C(C1=CC=C(C=C1)C)=O)=O.P(=O)(Cl)(Cl)Cl>>ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)C
O=[c:13]1[nH:12][c:11]2[cH:10][cH:9][c:8]([C:6]([c:5]3[cH:4][cH:3][c:2]([CH3:1])[cH:27][cH:26]3)=[O:7])[cH:25][c:24]2[c:16](-[c:17]2[cH:18][cH:19][cH:20][c:21]([Cl:22])[cH:23]2)[n:15]1.O=P(Cl)(Cl)[Cl:14]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][c:13]([Cl:14])[n:15][c:16](-[c:17]4[cH...
Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl
Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
O=C(c1ccccc1)c1ccc2ncnc(-c3ccccc3)c2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](:[c:7]):[nH;D2;+0:8]:1>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](:[c:7]):[n;H0;D2;+0:8]:1
70
[{"value": 70.0, "product": "ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)C", "details": "PERCENTYIELD", "is_desired": false}]
100
CELSIUS
4
HOUR
A mixture of intermediate 22 (0.041 mol) in phosphoryl chloride (105 ml) was stirred at 100° C. for 4 hours then cooled. The solvent was evaporated. The residue was taken up DCM. The solvent was evaporated. The residue was taken up in DCM. The mixture was poured out into ice water, basified with K2CO3 10% and extracted...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
HCl
null
100
4
Cc1ccc(C(=O)c2ccc3[nH]c(=O)nc(-c4cccc(Cl)c4)c3c2)cc1.O=P(Cl)(Cl)Cl>>Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c0c0c2a6fe664cd7b77993b86272439d
Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1>>Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
[Li]CCCC.Cl[Si](CC)(CC)CC.ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(=O)C1=CC=C(C=C1)C.[Li]CCCC.CN1C=NC=C1>>ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CC=C(C=C1)C)C1=CN=CN1C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11]3[n:12][c:13]([Cl:14])[n:15][c:16](-[c:17]4[cH:18][cH:19][cH:20][c:21]([Cl:22])[cH:23]4)[c:24]3[cH:25]2)[cH:32][cH:33]1.[cH:26]1[cH:27][n:28][cH:29][n:30]1[CH3:31]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([OH:7])([c:8]2[cH:9][cH:10][c:11]3[n:12][c:13]([C...
Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1
Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
null
null
O.C1CCOC1
C-C Coupling
OtherReaction
05395e7d28d1a7c287cdf9872044b38b254b469c1c451b45b37d37651dd6bc83
454f67ba8644982dc9f605915a0f36178771eadaffb50d3f1e0f17f2b6fdeb10
c1ccc(-c2ncnc3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[cH;D2;+0:6]:1.[O;H0;D1;+0:7]=[C;H0;D3;+0:8](-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]>>[C;D1;H3:1]-[#7;a:2]1:[c:3]:[#7;a:4]:[c:5]:[c;H0;D3;+0:6]:1-[C;H0;D4;+0:8](-[OH;D1;+0:7])(-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14]
null
[]
-70
CELSIUS
15
MINUTE
1-Methyl-1H-imidazole (0.0507 mol) was added at −70° C. to THF (90 ml) under N2 flow. nBuLi (31.5 ml) was added dropwise. The mixture was stirred at −70° C. for 15 minutes. Chlorotriethyl-silane (0.0522 mol) was added dropwise. The mixture was stirred at −70° C. for 15 minutes. nBuLi (28 ml) was added. The mixture was ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Tertiary alcohol
c1c[nH]cn1
c1c[nH]cn1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1.c1c[nH]cn1
null
O.C1CCOC1
-70
0.25
Cc1ccc(C(=O)c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)cc1.Cn1ccnc1>O.C1CCOC1>Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1fc055abe78a4989857da9219b7cb752
Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]>>Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
ClC1=NC2=CC=C(C=C2C(=N1)C1=CC(=CC=C1)Cl)C(O)(C1=CC=C(C=C1)C)C1=CN=CN1C.[N-]=[N+]=[N-].[Na+]>>ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2
Cl[c:23]1[n:22][c:14](-[c:15]2[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]2)[c:12]2[c:11]([cH:10][cH:9][c:8]([C:6]([c:5]3[cH:4][cH:3][c:2]([CH3:1])[cH:35][cH:34]3)([OH:7])[c:28]3[cH:29][n:30][cH:31][n:32]3[CH3:33])[cH:13]2)[n:27]1.[N-:24]=[N+:26]=[N-:25]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([OH:7])([c:8]2[cH:9][cH:10][...
Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]
Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
null
null
CN(C)C=O
Aromatic Heterocycle Formation
OtherReaction
4e0cb3e54897e660c5677e719a9c21ad2978ab17efb16dd9052e527979ac46a1
155f764f095c8454a4ad08aaa42f1abcb15d5bc1d4f122e4bcc624dd834362f2
c1ccc(-c2nc3nnnn3c3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5](:[c:6]):[n;H0;D2;+0:7]:1.[N-;H0;D1:8]=[N+;H0;D2:9]=[N-;H0;D1:10]>>[c:6]:[c:5]1:[c:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]2:[n;H0;D2;+0:8]:[n;H0;D2;+0:10]:[n;H0;D2;+0:9]:[n;H0;D3;+0:7]:1:2
72.7
[{"value": 72.7, "product": "ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
2
HOUR
A mixture of intermediate 24 (0.0105 mol) and sodium azide (0.031 mol) in DMF (70 ml) was stirred at 90° C. for 2 hours then cooled and poured out into ice water. The precipitate was filtered and taken up in DCM. The organic layer was washed with water, separated, dried (MgSO4), filtered, and the solvent was evaporated...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncncc2c1
c1ccc2c(c1)cnc1nnnn12
c1ccccc1.c1ccccc1.c1ccc2c(c1)cnc1nnnn12.c1c[nH]cn1
Other
CN(C)C=O
90
2
Cc1ccc(C(O)(c2ccc3nc(Cl)nc(-c4cccc(Cl)c4)c3c2)c2cncn2C)cc1.[N-]=[N+]=[N-]>CN(C)C=O>Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d1bbf580442944608dde689b3a7fc372
Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O=S(Cl)Cl>>Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.Cl
ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(O)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2.S(=O)(Cl)Cl>>Cl.ClC(C=1C=C2C(=NC=3N(C2=CC1)N=NN3)C3=CC(=CC=C3)Cl)(C3=CC=C(C=C3)C)C3=CN=CN3C
O[C:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:35][cH:34]1)([c:8]1[cH:9][cH:10][c:11]2[c:12]([cH:13]1)[c:14](-[c:15]1[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]1)[n:22][c:23]1[n:24][n:25][n:26][n:27]21)[c:28]1[cH:29][n:30][cH:31][n:32]1[CH3:33].O=S([Cl:7])[Cl:36]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([Cl:7])([c:8]2[cH:9][c...
Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O=S(Cl)Cl
Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.Cl
null
null
null
Functional Group Interconversion
Alcohol to chloride_SOCl2
6d9c985570d7a3f52661c667c74572d2f612d2c4fc81ba7e9dc85123f9e01aa3
8285cf7af1061d4e517653bb3812cef162cb49ef59cff39f31a19b6e110ce1b3
c1ccc(-c2nc3nnnn3c3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
O-[C;H0;D4;+0:1](-[c:2]1:[c:3]:[#7;a:4]:[c:5]:[#7;a:6]:1-[C;D1;H3:7])(-[c:8](:[c:9]):[c:10])-[c:11](:[c:12]):[c:13].O=S(-[Cl;H0;D1;+0:14])-[Cl;H0;D1;+0:15]>>[C;D1;H3:7]-[#7;a:6]1:[c:5]:[#7;a:4]:[c:3]:[c:2]:1-[C;H0;D4;+0:1](-[Cl;H0;D1;+0:15])(-[c:8](:[c:9]):[c:10])-[c:11](:[c:12]):[c:13].[ClH;D0;+0:14]
null
[]
60
CELSIUS
3
HOUR
A mixture of intermediate 25 (0.0083 mol) in thionyl chloride (80 ml) was stirred at 60° C. for 3 hours, then cooled and the solvent was evaporated. The residue was taken up in DCM. The solvent was evaporated, yielding 7-[chloro(1-methyl-1H-imidazol-5-yl)(4-methylphenyl)methyl]-5-(3-chlorophenyl)-tetrazolo[1,5-a]quinaz...
10.6084/m9.figshare.5104873.v1
null
Tertiary alcohol
Tertiary halide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)cnc1nnnn12.c1c[nH]cn1
Other
null
60
3
Cc1ccc(C(O)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O=S(Cl)Cl>>Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a3801d7d96d54cd2841fea0fa8ce85b6
CC(C)O.Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.N>>Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O
Cl.ClC(C=1C=C2C(=NC=3N(C2=CC1)N=NN3)C3=CC(=CC=C3)Cl)(C3=CC=C(C=C3)C)C3=CN=CN3C.N.CC(C)O>>O.ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2
CC(C)[OH:36].Cl[C:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:35][cH:34]1)([c:8]1[cH:9][cH:10][c:11]2[c:12]([cH:13]1)[c:14](-[c:15]1[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]1)[n:22][c:23]1[n:24][n:25][n:26][n:27]21)[c:28]1[cH:29][n:30][cH:31][n:32]1[CH3:33].[NH3:7]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([NH2:7])([c:8]2[cH:...
CC(C)O.Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.N
Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
cf04ad9dce2274e5d9a9cf24ee98c82defb9d00439b93dd2f2631fff7c8e202d
fb14544c66fca0b0883c6ebde415427401efbd881d01e0b9a902aed208e1aa10
c1ccc(-c2nc3nnnn3c3ccc(C(c4ccccc4)c4cnc[nH]4)cc23)cc1
C-C(-C)-[OH;D1;+0:1].Cl-[C;H0;D4;+0:2](-[c:3]1:[c:4]:[#7;a:5]:[c:6]:[#7;a:7]:1-[C;D1;H3:8])(-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14].[NH3;D0;+0:15]>>[C;D1;H3:8]-[#7;a:7]1:[c:6]:[#7;a:5]:[c:4]:[c:3]:1-[C;H0;D4;+0:2](-[NH2;D1;+0:15])(-[c:9](:[c:10]):[c:11])-[c:12](:[c:13]):[c:14].[OH2;D0;+0:1]
33
[{"value": 33.0, "product": "O.ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2", "details": "PERCENTYIELD", "is_desired": false}]
5
CELSIUS
1
HOUR
A mixture of intermediate 26 (0.0083 mol) in THF (80 ml) was cooled to 5° C. under N2 flow. NH3/iPrOH (80 ml) was added dropwise. The mixture was stirred at 5° C. for 1 hours, then brought to room temperature. The mixture was stirred at room temperature overnight, poured out into ice water and extracted with DCM. The o...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Secondary alcohol
Primary amine
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)cnc1nnnn12.c1c[nH]cn1
HCl
C1CCOC1
5
1
CC(C)O.Cc1ccc(C(Cl)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.N>C1CCOC1>Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1.O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8deae60c94284616a589f5ea5b9930c6
Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1>>Cc1ccc(C(N)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
C(Cl)Cl.[B-].[Na+].O.ClC=1C=C(C=CC1)C1=NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2>>ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2
[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([NH2:7])([c:8]2[cH:9][cH:10][c:11]3[c:12]([cH:13]2)[c:14](-[c:15]2[cH:16][cH:17][cH:18][c:19]([Cl:20])[cH:21]2)[n:22][c:23]2[n:24][n:25][n:26][n:27]32)[c:28]2[cH:29][n:30][cH:31][n:32]2[CH3:33])[cH:34][cH:35]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([C:6]([NH2:7])([c:8]2[cH:9][cH:10][c:11]3...
Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1
Cc1ccc(C(N)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
null
null
CO
Reduction
OtherReaction
68fa0e5ecb7fd022bbef2c0545f4aab67cdefa951d7696965b374d746a3ba330
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc(C2Nc3nnnn3-c3ccc(C(c4ccccc4)c4cnc[nH]4)cc32)cc1
[c:1]:[c:2]1:[c;H0;D3;+0:3](:[c:4]:[c:5]):[n;H0;D3;+0:6]2:[#7;a:7]:[#7;a:8]:[#7;a:9]:[c:10]:2:[n;H0;D2;+0:11]:[c;H0;D3;+0:12]:1-[c;H0;D3;+0:13](:[c:14]:[c:15]):[c:16]:[c:17]>>[c:1]:[c:2]1:[c;H0;D3;+0:3](:[c:4]:[c:5])-[n;H0;D3;+0:6]2:[#7;a:7]:[#7;a:8]:[#7;a:9]:[c:10]:2-[NH;D2;+0:11]-[CH;D3;+0:12]-1-[c;H0;D3;+0:13](:[c:1...
29
[{"value": 28.0, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.0, "product": "ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(N)(C1=CC=C(C=C1)C)C1=CN=CN1C)N=NN2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Sodium hydroborate (0.0005 mol) was added portionwise at room temperature to a mixture of intermediate 27 (0.0005 mol) in methanol (2.5 ml). The mixture was stirred at room temperature for 2 hours and poured out into ice water. DCM was added. The mixture was extracted with DCM. The organic layer was separated, washed w...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2c(c1)cnc1nnnn12
c1ccc2c(c1)CNc1nnnn12
c1ccccc1.c1ccccc1.c1ccc2c(c1)CNc1nnnn12.c1c[nH]cn1
null
CO
null
2
Cc1ccc(C(N)(c2ccc3c(c2)c(-c2cccc(Cl)c2)nc2nnnn23)c2cncn2C)cc1>CO>Cc1ccc(C(N)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-62b1e8b94e0e40819a548a7747a6c92b
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2>>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2
ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)N=NN2>>ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)=NN=N2
[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1)[c:16]1[cH:17][cH:18][c:19]2[c:20]([cH:21]1)[CH:22]([c:23]1[cH:24][cH:25][cH:26][c:27]([Cl:28])[cH:29]1)[NH:30][c:34]1[n:33][n:32][n:31][n:35]1-2>>[CH3:1][n:2]1[cH:3][n:4][cH:5][c:6]1[C:7]([OH:8])([c:9]1[cH:10][cH:11][c:...
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2
null
null
C1(=CC=CC=C1)C
Miscellaneous
OtherReaction
9cbfd0d2b6f07cab6074b89f8abb2208b435e69c8c7659d1f6d9527cea17dc98
5599dd978d687c53db7fabb5eef54650a477ffd906dc8d69ec8c4f7876adabe2
c1ccc(C(c2ccc3c(c2)C(c2ccccc2)n2nnnc2N3)c2cnc[nH]2)cc1
[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[C:6](-[c:7])-[NH;D2;+0:8]-[c:9]2:[#7;a:10]:[#7;a:11]:[n;H0;D2;+0:12]:[n;H0;D3;+0:13]:2-1>>[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[C:6](-[c:7])-[n;H0;D3;+0:8]2:[n;H0;D2;+0:12]:[#7;a:11]:[#7;a:10]:[c:9]:2-[NH;D2;+0:13]-1
51.2
[{"value": 50.0, "product": "ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)=NN=N2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.2, "product": "ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)F)=NN=N2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of intermediate 9 (0.0014 mol) in toluene (10 ml) was stirred and refluxed for 48 hours, then brought to room temperature and the solvent was evaporated till dryness. The residue was taken up in DCM. The solvent was evaporated till dryness. The residue was purified by column chromatography over kromasil® (10 ...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Secondary amine
c1ccc2c(c1)CNc1nnnn12
c1ccc2c(c1)Cn1nnnc1N2
c1cnc[nH]1.c1ccccc1.c1ccccc1.c1ccc2c(c1)Cn1nnnc1N2
null
C1(=CC=CC=C1)C
null
null
Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)Nc1nnnn1-2>C1(=CC=CC=C1)C>Cn1cncc1C(O)(c1ccc(F)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ee20223f472244bfac1603ceaa338f24
COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1>>COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)n2nnnc2N3)c2cncn2C)cc1
ClC=1C=C(C=CC1)C1NC=2N(C3=CC=C(C=C13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)N=NN2>>ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)=NN=N2
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH:10][cH:11][c:12]3[c:13]([cH:14]2)[CH:15]([c:16]2[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]2)[NH:23][c:27]2[n:26][n:25][n:24][n:28]2-3)[c:29]2[cH:30][n:31][cH:32][n:33]2[CH3:34])[cH:35][cH:36]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7]([OH:8])([c:9]2[cH:10][c...
COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1
COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)n2nnnc2N3)c2cncn2C)cc1
null
null
C1(=CC=CC=C1)C
Miscellaneous
OtherReaction
9cbfd0d2b6f07cab6074b89f8abb2208b435e69c8c7659d1f6d9527cea17dc98
5599dd978d687c53db7fabb5eef54650a477ffd906dc8d69ec8c4f7876adabe2
c1ccc(C(c2ccc3c(c2)C(c2ccccc2)n2nnnc2N3)c2cnc[nH]2)cc1
[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[C:6](-[c:7])-[NH;D2;+0:8]-[c:9]2:[#7;a:10]:[#7;a:11]:[n;H0;D2;+0:12]:[n;H0;D3;+0:13]:2-1>>[c:1]:[c:2]:[c;H0;D3;+0:3]1:[c:4](:[c:5])-[C:6](-[c:7])-[n;H0;D3;+0:8]2:[n;H0;D2;+0:12]:[#7;a:11]:[#7;a:10]:[c:9]:2-[NH;D2;+0:13]-1
27
[{"value": 27.0, "product": "ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)=NN=N2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 26.7, "product": "ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)OC)=NN=N2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of intermediate 17 (0.0006 mol) in toluene (10 ml) was stirred and refluxed for 5 hours, then brought to room temperature and the solvent, was evaporated till dryness. The residue was taken up in DCM. The solvent was evaporated till dryness. The residue was purified by column chromatography over kromasil® (10...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Secondary amine
c1ccc2c(c1)CNc1nnnn12
c1ccc2c(c1)Cn1nnnc1N2
c1ccccc1.c1ccccc1.c1ccc2c(c1)Cn1nnnc1N2.c1c[nH]cn1
null
C1(=CC=CC=C1)C
null
null
COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)Nc2nnnn2-3)c2cncn2C)cc1>C1(=CC=CC=C1)C>COc1ccc(C(O)(c2ccc3c(c2)C(c2cccc(Cl)c2)n2nnnc2N3)c2cncn2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f0885ae53cdd40c0bc3e07fc5ec6fe31
CCO.Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2.O>>COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
S(=O)(Cl)Cl.ClC=1C=C(C=CC1)C1N2C(NC=3C=CC(=CC13)C(O)(C1=CN=CN1C)C1=CC=C(C=C1)Cl)=NN=N2.CCO.O>>ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)OC
C[CH2:1][OH:2].Cn1cncc1[C:7]([c:6]1[cH:5][cH:4][c:3](Cl)[cH:26][cH:25]1)([OH:8])[c:9]1[cH:10][cH:11][c:12]2[c:23]([cH:24]1)[CH:15]([c:16]1[cH:17][cH:18][cH:19][c:20]([Cl:21])[cH:22]1)n1nnnc1[NH:13]2.[OH2:14]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[c:9]2[cH:10][cH:11][c:12]3[n:13][o:14][c:15](-[c:16]4[cH:17][...
CCO.Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2.O
COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
null
null
C(Cl)Cl
Acylation
OtherReaction
b68ed1a6e78323296df0c70e8a7f898f2bf257898deedcee227a2db14e9afb08
3f2ec67fe5b8665c3f7e857fb9a10a89e35b1acb414473f30dcf33bfc4774a11
O=C(c1ccccc1)c1ccc2noc(-c3ccccc3)c2c1
C-[CH2;D2;+0:1]-[OH;D1;+0:2].C-n1:c:n:c:c:1-[C;H0;D4;+0:3](-[OH;D1;+0:4])(-[c:5]1:[c:6]:[c:7]:[c;H0;D3;+0:8](-Cl):[c:9]:[c:10]:1)-[c:11]1:[c:12]:[c:13]:[c:14]2:[c:15](:[c:16]:1)-[CH;D3;+0:17](-[c;H0;D3;+0:18](:[c:19]:[c:20]):[c:21]:[c:22])-n1:n:n:n:c:1-[NH;D2;+0:23]-2.[OH2;D0;+0:24]>>[CH3;D1;+0:1]-[O;H0;D2;+0:2]-[c;H0;...
17
[{"value": 17.0, "product": "ClC=1C=C(C=CC1)C=1ON=C2C1C=C(C=C2)C(=O)C2=CC=C(C=C2)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Thionyl chloride (0.1 ml) was added at room temperature to a mixture of compound 1 (0.0002 mol) in EtOH (2 ml). The mixture was stirred at room temperature for 2 hours. Water was added. The mixture was taken up in DCM. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol.Tertiary alcohol.Secondary amine
Ketone.Ether
c1c[nH]cn1.c1ccccc1.c1ccc2c(c1)Cn1nnnc1N2
c1ccccc1.c1ccc2nocc2c1
c1ccccc1.c1ccc2nocc2c1.c1ccccc1
HCl
C(Cl)Cl
null
2
CCO.Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2c(c1)C(c1cccc(Cl)c1)n1nnnc1N2.O>C(Cl)Cl>COc1ccc(C(=O)c2ccc3noc(-c4cccc(Cl)c4)c3c2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e6dc98f870d84313bb53e8114f279824
O=C(O)C1(c2ccc(Cl)cc2)CCC1.OCC1CCCNC1>>O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1
N1CC(CCC1)CO.ClC1=CC=C(C=C1)C1(CCC1)C(=O)O.C(C)(C)N(CC)C(C)C.C1CCN(C1)[P+](N2CCCC2)(N3CCCC3)Br.F[P-](F)(F)(F)(F)F>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CO
O[C:2](=[O:1])[C:11]1([c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:19][CH2:20][CH2:21]1.[NH:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][OH:9])[CH2:10]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][OH:9])[CH2:10]1)[C:11]1([c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:19][CH2:20][CH2:21]1
O=C(O)C1(c2ccc(Cl)cc2)CCC1.OCC1CCCNC1
O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1
null
null
ClCCl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
fbfce93ec1ece674255bb96c5cec09ad611382b41cf117dfe580015e21744a71
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(N1CCCCC1)C1(c2ccccc2)CCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])(-[C:5])-[C:6].[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]>>[C:5]-[C:3](-[c:4])(-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9](-[C:10]-[C:11])-[C:8]-[C:7])-[C:6]
43.4
[{"value": 43.4, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
To a solution of 3-piperidinemethanol (5.0 g, 43.4 mmol), 1-(4-chlorophenyl)-1-cyclobutanecarboxylic acid (9.14 g, 43.4 mmol), and diisopropylethylamine (11.22 g, 86.8 mmol) in dichloromethane (100 mL) at 0° C. was added PyBroP® (22.26 g, 47.8 mmol). The reaction was stirred at 0° C. for 1 h and then at room temperatur...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1.C1CCC1
HO-
ClCCl
0
1
O=C(O)C1(c2ccc(Cl)cc2)CCC1.OCC1CCCNC1>ClCCl>O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1c0863060bf5429485d5a823cc840c77
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1>>CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CO.C(C)N(CC)CC.CS(=O)(=O)Cl>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C
Cl[S:2]([CH3:1])(=[O:3])=[O:4].[OH:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2:10][N:11]([C:12](=[O:13])[C:14]2([c:15]3[cH:16][cH:17][c:18]([Cl:19])[cH:20][cH:21]3)[CH2:22][CH2:23][CH2:24]2)[CH2:25]1>>[CH3:1][S:2](=[O:3])(=[O:4])[O:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2:10][N:11]([C:12](=[O:13])[C:14]2([c:15]3[cH:16][cH:17][c:18]([...
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
null
null
ClCCl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
O=C(N1CCCCC1)C1(c2ccccc2)CCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
71
[{"value": 71.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.7, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
The amide derivative 1 (5.0 g, 16.3 mmol) was dissolved in dichloromethane (50 mL) and cooled to 0° C. To this solution was added triethylamine (5.0 mL) followed by dropwise addition of methanesulfonyl chloride (2.05 g, 17.9 mmol). The reaction was stirred at 0 C. for 1 h, and then at room temperature overnight. The re...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
C1CC[NH]CC1.c1ccccc1.C1CCC1
HCl
ClCCl
0
1
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCC1>ClCCl>CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8f55b5e0e1b34aed9a393af46d3bc746
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1>>COc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.COC1=C(C=CC=C1)N1CCNCC1.C(C)N(CC)CC>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[CH2:10][CH2:11][NH:12][CH2:33][CH2:34]1.CS(=O)(=O)O[CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][N:18]([C:19](=[O:20])[C:21]2([c:22]3[cH:23][cH:24][c:25]([Cl:26])[cH:27][cH:28]3)[CH2:29][CH2:30][CH2:31]2)[CH2:32]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[...
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
COc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Alkylation of amines
1bf281a76f5d92191240c4561d80a265a934eb351041bae69548607f60e915b2
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
43.1
[{"value": 43.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.1, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2 (1.0 g, 2.60 mmol) in acetonitrile (25 mL) was added 1-(2-methoxyphenyl)piperazine (0.55 g, 2.86 mmol) and triethylamine (2 mL). The reaction was stirred and refluxed for 20 h. After cooling to room temperature, most of solvent was removed by rotary evaporation. The reaction mixture was partitioned b...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.C1CC[NH]CC1.c1ccccc1.C1CCC1
MsOH.HO-
C(C)#N
null
null
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1>C(C)#N>COc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-839499243f7b4daead6dc6bd98c0c6c8
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Clc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3Cl)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.ClC1=C(C=CC=C1)N1CCNCC1.C([O-])([O-])=O.[Cs+].[Cs+]>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)Cl
CS(=O)(=O)O[CH2:8][CH:7]1[CH2:6][CH2:5][CH2:4][N:3]([C:2](=[O:1])[C:23]2([c:24]3[cH:25][cH:26][c:27]([Cl:28])[cH:29][cH:30]3)[CH2:31][CH2:32][CH2:33]2)[CH2:22]1.[NH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH:15][cH:16][cH:17][c:18]2[Cl:19])[CH2:20][CH2:21]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][N:9]2[...
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Clc1ccccc1N1CCNCC1
O=C(N1CCCC(CN2CCN(c3ccccc3Cl)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
null
null
null
Heteroatom Alkylation and Arylation
Alkylation of amines
bc40e881c80f733cc18ae6a4c32c0d2e3ac9ce7b07d3a2cb609684e869dc6007
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
42
[{"value": 42.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 41.9, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound 7 was prepared using the method of described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-chlorophenyl)piperazine (0.56 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 7 (0.53 g, 42%); C27H33Cl2N3O, LRMS (m/z)=487 (MH+). Conditions: See reaction.notes.procedure_details. Worku...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.C1CCC1
MsOH.HO-
null
null
null
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Clc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3Cl)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e6d3ae6968eb4aeebe2edddb0e93582c
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Fc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.FC1=C(C=CC=C1)N1CCNCC1.C([O-])([O-])=O.[Cs+].[Cs+]>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)F
CS(=O)(=O)O[CH2:8][CH:7]1[CH2:6][CH2:5][CH2:4][N:3]([C:2](=[O:1])[C:23]2([c:24]3[cH:25][cH:26][c:27]([Cl:28])[cH:29][cH:30]3)[CH2:31][CH2:32][CH2:33]2)[CH2:22]1.[NH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH:15][cH:16][cH:17][c:18]2[F:19])[CH2:20][CH2:21]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][N:9]2[C...
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Fc1ccccc1N1CCNCC1
O=C(N1CCCC(CN2CCN(c3ccccc3F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
null
null
null
Heteroatom Alkylation and Arylation
Alkylation of amines
bc40e881c80f733cc18ae6a4c32c0d2e3ac9ce7b07d3a2cb609684e869dc6007
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
46
[{"value": 46.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.8, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound 8 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-fluorophenyl)piperazine (0.51 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 8 (0.56 g, 46%); C27H33ClFN3O, LRMS (m/z)=471 (MH+). Conditions: See reaction.notes.procedure_details. Workup: ...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.C1CCC1
MsOH.HO-
null
null
null
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Fc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1eff77d0a8f94fd79d80d99e54259ac7
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.FC(F)(F)Oc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3OC(F)(F)F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.FC(OC1=C(C=CC=C1)N1CCNCC1)(F)F.C([O-])([O-])=O.[Cs+].[Cs+]>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(F)(F)F
CS(=O)(=O)O[CH2:8][CH:7]1[CH2:6][CH2:5][CH2:4][N:3]([C:2](=[O:1])[C:27]2([c:28]3[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]3)[CH2:35][CH2:36][CH2:37]2)[CH2:26]1.[NH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH:15][cH:16][cH:17][c:18]2[O:19][C:20]([F:21])([F:22])[F:23])[CH2:24][CH2:25]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][...
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.FC(F)(F)Oc1ccccc1N1CCNCC1
O=C(N1CCCC(CN2CCN(c3ccccc3OC(F)(F)F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
null
null
null
Heteroatom Alkylation and Arylation
Alkylation of amines
bc40e881c80f733cc18ae6a4c32c0d2e3ac9ce7b07d3a2cb609684e869dc6007
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
32.3
[{"value": 32.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 32.3, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound 9 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-trifluoromethoxyphenyl)piperazine (0.70 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 9 (0.45 g, 32%); C28H33ClF3N3O2, LRMS (m/z)=537 (MH+). Conditions: See reaction.notes.procedure_detai...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.C1CCC1
MsOH.HO-
null
null
null
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.FC(F)(F)Oc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3OC(F)(F)F)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e826ef96d0254473a066b1b2039e0662
CC(C)Oc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1>>CC(C)Oc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.C(C)(C)OC1=C(C=CC=C1)N1CCNCC1.C([O-])([O-])=O.[Cs+].[Cs+]>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(C)C
[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[N:11]1[CH2:12][CH2:13][NH:14][CH2:35][CH2:36]1.CS(=O)(=O)O[CH2:15][CH:16]1[CH2:17][CH2:18][CH2:19][N:20]([C:21](=[O:22])[C:23]2([c:24]3[cH:25][cH:26][c:27]([Cl:28])[cH:29][cH:30]3)[CH2:31][CH2:32][CH2:33]2)[CH2:34]1>>[CH3:1][CH:2]([CH3:3])[O:4][c:5]1[cH:6...
CC(C)Oc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1
CC(C)Oc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
null
null
null
Heteroatom Alkylation and Arylation
Alkylation of amines
1bf281a76f5d92191240c4561d80a265a934eb351041bae69548607f60e915b2
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
37
[{"value": 37.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.9, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound 11 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-isopropoxyphenyl)piperazine (0.63 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 11 (0.49 g, 37%); C30H40ClN3O2, LRMS (m/z)=511 (MH+). Conditions: See reaction.notes.procedure_details. Wo...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.C1CC[NH]CC1.c1ccccc1.C1CCC1
MsOH.HO-
null
null
null
CC(C)Oc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1>>CC(C)Oc1ccccc1N1CCN(CC2CCCN(C(=O)C3(c4ccc(Cl)cc4)CCC3)C2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-84a165eb047144dd97ead8cb0ccc328c
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Oc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3O)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C.OC1=C(C=CC=C1)N1CCNCC1.C([O-])([O-])=O.[Cs+].[Cs+]>>ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)O
CS(=O)(=O)O[CH2:8][CH:7]1[CH2:6][CH2:5][CH2:4][N:3]([C:2](=[O:1])[C:23]2([c:24]3[cH:25][cH:26][c:27]([Cl:28])[cH:29][cH:30]3)[CH2:31][CH2:32][CH2:33]2)[CH2:22]1.[NH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH:15][cH:16][cH:17][c:18]2[OH:19])[CH2:20][CH2:21]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][N:9]2[...
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Oc1ccccc1N1CCNCC1
O=C(N1CCCC(CN2CCN(c3ccccc3O)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
null
null
null
Heteroatom Alkylation and Arylation
Alkylation of amines
bc40e881c80f733cc18ae6a4c32c0d2e3ac9ce7b07d3a2cb609684e869dc6007
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
O=C(N1CCCC(CN2CCN(c3ccccc3)CC2)C1)C1(c2ccccc2)CCC1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
32
[{"value": 32.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 32.0, "product": "ClC1=CC=C(C=C1)C1(CCC1)C(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Compound 12 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-hydroxyphenyl)piperazine (0.51 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 12 (0.39 g, 32%); C27H34ClN3O2, LRMS (m/z)=469 (MH+). Conditions: See reaction.notes.procedure_details. Worku...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1CC[NH]CC1.C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.C1CCC1
MsOH.HO-
null
null
null
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCC2)C1.Oc1ccccc1N1CCNCC1>>O=C(N1CCCC(CN2CCN(c3ccccc3O)CC2)C1)C1(c2ccc(Cl)cc2)CCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1de4723cb91b4f48ba6cf29426e8ae90
CC(C)(C)OC(=O)N1CCCC(CO)C1.CS(=O)(=O)Cl>>CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1
CS(=O)(=O)Cl.C(C)(C)(C)OC(=O)N1CC(CCC1)CO.CCN(C(C)C)C(C)C>>C(C)(C)(C)OC(=O)N1CC(CCC1)COS(=O)(=O)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][CH:12]([CH2:13][OH:14])[CH2:19]1.Cl[S:15]([CH3:16])(=[O:17])=[O:18]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][CH:12]([CH2:13][O:14][S:15]([CH3:16])(=[O:17])=[O:18])[CH2:19]1
CC(C)(C)OC(=O)N1CCCC(CO)C1.CS(=O)(=O)Cl
CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1
null
null
ClCCl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
C1CCNCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
86
[{"value": 86.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (9.41 g, 0.048 mol) in dichloromethane (200 mL) at room temperature was added iPr2NEt (14.1 g, 0.110 mol), followed by MsCl (5.5 g, 0.048 mol). The reaction mixture was allowed to stir for one hour before concentrating and purifying the resu...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
C1CC[NH]CC1
HCl
ClCCl
null
1
CC(C)(C)OC(=O)N1CCCC(CO)C1.CS(=O)(=O)Cl>ClCCl>CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-987342903f5641e0bac10390d6fc29ed
CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1.COc1ccccc1N1CCNCC1>>COc1ccccc1N1CCN(CC2CCCN(C(=O)OC(C)(C)C)C2)CC1
COC1=C(C=CC=C1)N1CCNCC1.C(C)(C)(C)OC(=O)N1CC(CCC1)COS(=O)(=O)C.C([O-])([O-])=O.[K+].[K+]>>C(C)(C)(C)OC(=O)N1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC
CS(=O)(=O)O[CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][N:18]([C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:26]1.[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[CH2:10][CH2:11][NH:12][CH2:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[CH2:10][CH2:11][N:12]([CH2:13][CH:14]2[CH2:15...
CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1.COc1ccccc1N1CCNCC1
COc1ccccc1N1CCN(CC2CCCN(C(=O)OC(C)(C)C)C2)CC1
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Alkylation of amines
1bf281a76f5d92191240c4561d80a265a934eb351041bae69548607f60e915b2
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
c1ccc(N2CCN(CC3CCCNC3)CC2)cc1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
null
[]
null
null
null
null
To a solution of 3-methanesulfonyloxymethyl-piperidine-1-carboxylic acid tert-butyl ester (11.06 g, 0.04 mol) in acetonitrile (180 mL) was added potassium carbonate (26 g, 0.19 mol) followed by 1-(2-methoxy-phenyl) piperazine (7.25 g, 0.04 mol). After completion of addition the reaction mixture was heated to reflux. Af...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.C1CC[NH]CC1
MsOH.HO-
C(C)#N
null
null
CC(C)(C)OC(=O)N1CCCC(COS(C)(=O)=O)C1.COc1ccccc1N1CCNCC1>C(C)#N>COc1ccccc1N1CCN(CC2CCCN(C(=O)OC(C)(C)C)C2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3d2ddcff4e1c4aee8e997e55b2747644
O=C(O)C1(c2ccc(Cl)cc2)CCCC1.OCC1CCCNC1>>O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1
C1CCN(C1)[P+](N2CCCC2)(N3CCCC3)Br.F[P-](F)(F)(F)(F)F.N1CC(CCC1)CO.ClC1=CC=C(C=C1)C1(CCCC1)C(=O)O.C(C)(C)N(CC)C(C)C>>ClC1=CC=C(C=C1)C1(CCCC1)C(=O)N1CC(CCC1)CO
O[C:2](=[O:1])[C:11]1([c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:19][CH2:20][CH2:21][CH2:22]1.[NH:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][OH:9])[CH2:10]1>>[O:1]=[C:2]([N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([CH2:8][OH:9])[CH2:10]1)[C:11]1([c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:19][CH2:20][CH2:2...
O=C(O)C1(c2ccc(Cl)cc2)CCCC1.OCC1CCCNC1
O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1
null
null
ClCCl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
fbfce93ec1ece674255bb96c5cec09ad611382b41cf117dfe580015e21744a71
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(N1CCCCC1)C1(c2ccccc2)CCCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])(-[C:5])-[C:6].[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]>>[C:5]-[C:3](-[c:4])(-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9](-[C:10]-[C:11])-[C:8]-[C:7])-[C:6]
156.9
[{"value": 156.9, "product": "ClC1=CC=C(C=C1)C1(CCCC1)C(=O)N1CC(CCC1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of piperdin-3-yl methanol (0.342 g, 2.97 mmol), 1-(4-chloro-phenyl)-cyclopentylcarboxylic acid (1.0 g, 4.45 mmol), diisopropylethyl amine (1.9, 15.00 mmol) in dichloromethane (7 mL) was stirred at room temperature. PyBroP (2.07 g, 4.45 mmol) was added and the reaction mixture continued stirring at room tempe...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1.C1CCCC1
HO-
ClCCl
null
null
O=C(O)C1(c2ccc(Cl)cc2)CCCC1.OCC1CCCNC1>ClCCl>O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c5434389f3a442329f8bdc103ff7daa9
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1>>CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCCC2)C1
CS(=O)(=O)Cl.ClC1=CC=C(C=C1)C1(CCCC1)C(=O)N1CC(CCC1)CO.CCN(C(C)C)C(C)C>>ClC1=CC=C(C=C1)C1(CCCC1)C(=O)N1CC(CCC1)COS(=O)(=O)C
Cl[S:2]([CH3:1])(=[O:3])=[O:4].[OH:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2:10][N:11]([C:12](=[O:13])[C:14]2([c:15]3[cH:16][cH:17][c:18]([Cl:19])[cH:20][cH:21]3)[CH2:22][CH2:23][CH2:24][CH2:25]2)[CH2:26]1>>[CH3:1][S:2](=[O:3])(=[O:4])[O:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2:10][N:11]([C:12](=[O:13])[C:14]2([c:15]3[cH:16][cH:17]...
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1
CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCCC2)C1
null
null
ClCCl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
O=C(N1CCCCC1)C1(c2ccccc2)CCCC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
56
[{"value": 56.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of [1-(4-chloro-phenyl)-cyclopentyl]-(3-hydroxymethyl-piperidin-1-yl)-methanone (0.5 g, 1.55 mmol) in dichloromethane (9.5 mL) at room temperature was added iPr2NEt (0.5 g, 3.9 mmol) followed by MsCl (0.214 g, 1.86 mmol). The reaction mixture was allowed to stir for one hour before concentrating and purif...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
C1CC[NH]CC1.c1ccccc1.C1CCCC1
HCl
ClCCl
null
1
CS(=O)(=O)Cl.O=C(N1CCCC(CO)C1)C1(c2ccc(Cl)cc2)CCCC1>ClCCl>CS(=O)(=O)OCC1CCCN(C(=O)C2(c3ccc(Cl)cc3)CCCC2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-126bbfff893842e280cfbd2c99e113f0
CCOC(=O)C1CCCNC1.O=C(O)C1(c2ccc(Cl)cc2)CC1>>CCOC(=O)C1CCCN(C(=O)C2(c3ccc(Cl)cc3)CC2)C1
C1CCN(C1)[P+](N2CCCC2)(N3CCCC3)Br.F[P-](F)(F)(F)(F)F.C(C)OC(=O)C1CNCCC1.ClC1=CC=C(C=C1)C1(CC1)C(=O)O.C(C)(C)N(CC)C(C)C>>C(C)OC(=O)C1CN(CCC1)C(=O)C1(CC1)C1=CC=C(C=C1)Cl
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][CH2:9][NH:10][CH2:23]1.O[C:11](=[O:12])[C:13]1([c:14]2[cH:15][cH:16][c:17]([Cl:18])[cH:19][cH:20]2)[CH2:21][CH2:22]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][CH2:9][N:10]([C:11](=[O:12])[C:13]2([c:14]3[cH:15][cH:16][c:17]([Cl:18])[cH:19][cH:20]3)[CH2:2...
CCOC(=O)C1CCCNC1.O=C(O)C1(c2ccc(Cl)cc2)CC1
CCOC(=O)C1CCCN(C(=O)C2(c3ccc(Cl)cc3)CC2)C1
null
null
ClCCl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
fbfce93ec1ece674255bb96c5cec09ad611382b41cf117dfe580015e21744a71
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(N1CCCCC1)C1(c2ccccc2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1(-[c:4])-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]>>[#8:7]-[C:8](=[O;D1;H0:9])-[C:10]-[C:11]-[N;H0;D3;+0:12](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1(-[c:4])-[C:5]-[C:6]-1)-[C:13]-[C:14]
167.5
[{"value": 167.5, "product": "C(C)OC(=O)C1CN(CCC1)C(=O)C1(CC1)C1=CC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of piperidine-3-carboxylic acid ethyl ester (10.0 g, 0.032 mol), 1-(4-chloro-phenyl)-cyclopropylcarboxylic acid (9.57 g, 0.049 mol), diisopropylethyl amine (21.0 g, 0.16 mol) in dichloromethane (160 mL) was stirred at room temperature. PyBroP (22.6 g, 0.49 mol) was added and the reaction mixture continued st...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1.C1CC1
HO-
ClCCl
null
null
CCOC(=O)C1CCCNC1.O=C(O)C1(c2ccc(Cl)cc2)CC1>ClCCl>CCOC(=O)C1CCCN(C(=O)C2(c3ccc(Cl)cc3)CC2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eeb8b540ab9d40e081dbf145739db960
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(CC2(c3ccc(Cl)cc3)CC2)C1>>COc1ccccc1N1CCN(CC2CCCN(CC3(c4ccc(Cl)cc4)CC3)C2)CC1
C([O-])([O-])=O.[K+].[K+].ClC1=CC=C(C=C1)C1(CC1)CN1CC(CCC1)COS(=O)(=O)C.COC1=C(C=CC=C1)N1CCNCC1>>ClC1=CC=C(C=C1)C1(CC1)CN1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[CH2:10][CH2:11][NH:12][CH2:31][CH2:32]1.CS(=O)(=O)O[CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][N:18]([CH2:19][C:20]2([c:21]3[cH:22][cH:23][c:24]([Cl:25])[cH:26][cH:27]3)[CH2:28][CH2:29]2)[CH2:30]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[N:9]1[CH2:10][CH2:11]...
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(CC2(c3ccc(Cl)cc3)CC2)C1
COc1ccccc1N1CCN(CC2CCCN(CC3(c4ccc(Cl)cc4)CC3)C2)CC1
null
null
O.C(C)#N
Heteroatom Alkylation and Arylation
Alkylation of amines
1bf281a76f5d92191240c4561d80a265a934eb351041bae69548607f60e915b2
35d789812c3241c3a185d06663a309d930259e30563212f3884ef74718436cbc
c1ccc(N2CCN(CC3CCCN(CC4(c5ccccc5)CC4)C3)CC2)cc1
C-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#7:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#7:6]-[C:11]-[C:10]-1)-[C:3]
54.8
[{"value": 54.8, "product": "ClC1=CC=C(C=C1)C1(CC1)CN1CC(CCC1)CN1CCN(CC1)C1=C(C=CC=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of methanesulfonic acid 1-[1-(4-chloro-phenyl)-cyclopropylmethyl]-piperidin-3-ylmethyl ester (2.94 g, 8.20 mmol) in acetonitrile (40.0 mL) at room temperature was added 1-(2-methoxy-phenyl)-piperazine (1.58 g, 8.20 mmol) followed by potassium carbonate (13.35 g, 41.0 mmol). The reaction mixture was reflux...
10.6084/m9.figshare.5104873.v1
null
Mesylate.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.C1CC[NH]CC1.c1ccccc1.C1CC1
MsOH.HO-
O.C(C)#N
null
null
COc1ccccc1N1CCNCC1.CS(=O)(=O)OCC1CCCN(CC2(c3ccc(Cl)cc3)CC2)C1>O.C(C)#N>COc1ccccc1N1CCN(CC2CCCN(CC3(c4ccc(Cl)cc4)CC3)C2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0dbd4d7198d1482db8cfa43ccca46c06
CCc1ccc(CCO)nc1.CS(=O)(=O)Cl.Cc1ccccc1>>CCc1ccc(CCOc2ccc(C=O)cc2)nc1
C(C)C=1C=CC(=NC1)CCO.C(C)N(CC)CC.C1(=CC=CC=C1)C.CS(=O)(=O)Cl>>C(C)C=1C=CC(=NC1)CCOC1=CC=C(C=O)C=C1
[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][OH:9])[n:18][cH:19]1.CS(=O)(Cl)=[O:15].[c:10]1([CH3:14])[cH:11][cH:12][cH:13][cH:16][cH:17]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][c:13]([CH:14]=[O:15])[cH:16][cH:17]2)[n:18][cH:19]1
CCc1ccc(CCO)nc1.CS(=O)(=O)Cl.Cc1ccccc1
CCc1ccc(CCOc2ccc(C=O)cc2)nc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
8135fceb97f19207e61861f22c88d41660fa03834381f75b5a09e5f0f896399b
ef7b7af1598f102ca0aae078b932ae9b72819eb1ae7b4b40e631ef4d878456f8
c1ccc(OCCc2ccccn2)cc1
C-S(-Cl)(=O)=[O;H0;D1;+0:1].[CH3;D1;+0:2]-[c;H0;D3;+0:3]1:[c:4]:[c:5]:[cH;D2;+0:6]:[c:7]:[c:8]:1.[C:9]-[C:10]-[OH;D1;+0:11]>>[C:9]-[C:10]-[O;H0;D2;+0:11]-[c;H0;D3;+0:3]1:[c:4]:[c:5]:[c;H0;D3;+0:6](-[CH;D2;+0:2]=[O;H0;D1;+0:1]):[c:7]:[c:8]:1
null
[]
null
null
1
HOUR
10 g of 5-ethyl-2-pyridine ethanol, 10.2 ml triethylamine and 75 ml toluene are added to the round bottom assembly at ambient temperature. Thereafter 6.16 ml methane sulfonyl chloride are added via dropping funnel in 1 hour. The reaction mixture is stirred at ambient temperature for 1 hour and then washed with water. T...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Aldehyde.Ether
c1ccccc1
c1ccccc1
c1ccncc1.c1ccccc1
HCl
null
null
1
CCc1ccc(CCO)nc1.CS(=O)(=O)Cl.Cc1ccccc1>>CCc1ccc(CCOc2ccc(C=O)cc2)nc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-22689c6094034a408671349ef7f00a54
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1>>O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
BrC1=C(C=CC(=C1)[N+](=O)[O-])F.[F-].[K+].FC(OC1=C(C=C(C=O)C=C1)O)F>>FC(OC1=C(C=C(C=O)C=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])Br)F
[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([O:7][CH:8]([F:9])[F:10])[c:11]([OH:12])[cH:23]1.F[c:13]1[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][c:21]1[Br:22]>>[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([O:7][CH:8]([F:9])[F:10])[c:11]([O:12][c:13]2[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][c:21]2[Br:22])[cH:23]1
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1
O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
e4ea1e38252bc3b9c5ec04486386725e6570ab3860d45e337a1d131319bbf0fc
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(Oc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[Br;D1;H0:5]):[c:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[Br;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]):[c:2]:[c:3]
null
[]
null
null
null
null
According to other embodiments, the present invention provides methods of preparing N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfoneamide-dibenzo[b,d]furan-1-carboxamide comprising the steps of: (a) reacting 4-difluoromethoxy-3-hydroxybenzaldehyde with 2-bromo-1-fluoro-4-nitrobenzene in a first solvent com...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
null
null
null
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1>>O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-715f96d68ecf4b60b50b33ade046d8dd
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1>>O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
[F-].[K+].FC(OC1=C(C=C(C=O)C=C1)O)F.BrC1=C(C=CC(=C1)[N+](=O)[O-])F>>FC(OC1=C(C=C(C=O)C=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])Br)F
[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([O:7][CH:8]([F:9])[F:10])[c:11]([OH:12])[cH:23]1.F[c:13]1[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][c:21]1[Br:22]>>[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([O:7][CH:8]([F:9])[F:10])[c:11]([O:12][c:13]2[cH:14][cH:15][c:16]([N+:17](=[O:18])[O-:19])[cH:20][c:21]2[Br:22])[cH:23]1
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1
O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
e4ea1e38252bc3b9c5ec04486386725e6570ab3860d45e337a1d131319bbf0fc
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(Oc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[Br;D1;H0:5]):[c:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[Br;D1;H0:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]):[c:2]:[c:3]
null
[]
null
null
null
null
In other embodiments, the present invention provides methods of preparing N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamide-dibenzo[b,d]furan-1-carboxamide, as shown in FIG. 1. For example, 4-difluoromethoxy-3-hydroxybenzaldehyde may be reacted with 2-bromo-1-fluoro-4-nitrobenzene in a first solvent com...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
null
null
null
O=Cc1ccc(OC(F)F)c(O)c1.O=[N+]([O-])c1ccc(F)c(Br)c1>>O=Cc1ccc(OC(F)F)c(Oc2ccc([N+](=O)[O-])cc2Br)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0079d10c0e9d474da7f472c866bc5163
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl.[In].ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl.[In].[In]>>ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)N)OC(F)F)Cl
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH:18][c:19]4[c:20]([Cl:21])[cH:22][n:23][cH:24][c:25]4[Cl:26])[c:27]3[c:28]2[cH:29]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH...
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
null
null
[Cl-].[NH4+].[NH4+].[Cl-].C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(Nc1ccncc1)c1cccc2oc3ccccc3c12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
80
CELSIUS
null
null
First, N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-aminodibenzo[b,d]furan-1-carboxamide was prepared by reacting N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (prepared using the procedure of Example 4) with indium in ethanol and saturated ammonium chloride. To a 1 L 3-neck rou...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2c(c1)oc1ccccc12.c1ccncc1
Other
[Cl-].[NH4+].[NH4+].[Cl-].C(C)O
80
null
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>[Cl-].[NH4+].[NH4+].[Cl-].C(C)O>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6b0e8e1cb5944cfeb487d069970659bb
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl>>ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)N)OC(F)F)Cl
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH:18][c:19]4[c:20]([Cl:21])[cH:22][n:23][cH:24][c:25]4[Cl:26])[c:27]3[c:28]2[cH:29]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH...
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
null
[Ni].[Ni]
CN(C)C=O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(Nc1ccncc1)c1cccc2oc3ccccc3c12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
91.3
[{"value": 91.3, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Second, N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-aminodibenzo[b,d]furan-1-carboxamide was prepared by reacting N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (prepared using the procedure of Example 4) with Raney Nickel. In particular, to a 500 mL pressure vessel was added N′...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2c(c1)oc1ccccc12.c1ccncc1
Other
[Ni].[Ni].CN(C)C=O
null
null
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>[Ni].[Ni].CN(C)C=O>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-824f639efe49499785302908ee443f3a
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
[Cl-].[NH4+].ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl>>ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)N)OC(F)F)Cl
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH:18][c:19]4[c:20]([Cl:21])[cH:22][n:23][cH:24][c:25]4[Cl:26])[c:27]3[c:28]2[cH:29]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH...
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
null
[Zn].[Zn]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(Nc1ccncc1)c1cccc2oc3ccccc3c12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
79.4
[{"value": 79.4, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
Third, N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-aminodibenzo[b,d]furan-1-carboxamide was prepared by reacting N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (prepared using the procedure of Example 4) with zinc. In particular, to a 250 mL 2-necked round bottom flask was added...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2c(c1)oc1ccccc12.c1ccncc1
Other
[Zn].[Zn].C(C)O
95
null
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>[Zn].[Zn].C(C)O>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e144463b449443ad8ea96c41bd4203b8
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl.ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)[N+](=O)[O-])OC(F)F)Cl.Cl.[BH4-].[Na+].[BH4-].[Na+]>>ClC=1C=NC=C(C1NC(=O)C1=CC=C(C=2OC3=C(C21)C=C(C=C3)N)OC(F)F)Cl
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH:18][c:19]4[c:20]([Cl:21])[cH:22][n:23][cH:24][c:25]4[Cl:26])[c:27]3[c:28]2[cH:29]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[o:6][c:7]3[c:8]([O:9][CH:10]([F:11])[F:12])[cH:13][cH:14][c:15]([C:16](=[O:17])[NH...
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12
Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
null
[Pd].[Pd]
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(Nc1ccncc1)c1cccc2oc3ccccc3c12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
7.5
CELSIUS
null
null
Fourth, N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-aminodibenzo[b,d]furan-1-carboxamide was prepared by reacting N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (prepared using the procedure of Example 4) with sodium borohydride in methanol and palladium on carbon (50% wet with ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2c(c1)oc1ccccc12.c1ccncc1
Other
[Pd].[Pd].CO
7.5
null
O=C(Nc1c(Cl)cncc1Cl)c1ccc(OC(F)F)c2oc3ccc([N+](=O)[O-])cc3c12>[Pd].[Pd].CO>Nc1ccc2oc3c(OC(F)F)ccc(C(=O)Nc4c(Cl)cncc4Cl)c3c2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9d32e44336ab474fa7ed89bdaf146243
COc1ccccc1Cl.O=C(Cl)CCCl>>COc1cc2c(cc1Cl)C(=O)CC2
S(O)(O)(=O)=O.ClC1=C(C=CC=C1)OC.ClCCC(=O)Cl.[Al+3].[Cl-].[Cl-].[Cl-]>>ClC1=C(C=C2CCC(C2=C1)=O)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[Cl:9].Cl[C:10](=[O:11])[CH2:12][CH2:13]Cl>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([cH:7][c:8]1[Cl:9])[C:10](=[O:11])[CH2:12][CH2:13]2
COc1ccccc1Cl.O=C(Cl)CCCl
COc1cc2c(cc1Cl)C(=O)CC2
null
null
C(Cl)Cl
C-C Coupling
OtherReaction
54e4063f482a505c1566def1ae70d791f57b6a30eeb317d048d2c7802bd26423
4891bfec14a44c572847b13e296d05d3abe17c47adfe6f321080d329be8991f3
O=C1CCc2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]-[C;H0;D3;+0:3](-Cl)=[O;D1;H0:4].[c:5]1:[c:6]:[cH;D2;+0:7]:[cH;D2;+0:8]:[c:9]:[c:10]:1>>[O;D1;H0:4]=[C;H0;D3;+0:3]1-[C:2]-[CH2;D2;+0:1]-[c;H0;D3;+0:7]2:[c:6]:[c:5]:[c:10]:[c:9]:[c;H0;D3;+0:8]:2-1
null
[]
100
CELSIUS
30
MINUTE
To a solution of 1-chloro-2-methoxybenzene (12.8 mL, 100 mmol) and 3-chloropropanoyl chloride (10.5 mL, 110 mmol) in CH2Cl2 (100 mL) at 0° C. was added AlCl3 (14.6 g, 110 mmol) portionwise during about 1 minute. After 30 minutes, sulfuric acid (300 mL) was poured slowly into the reaction mixture during about 3 minutes....
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary halide
Ketone
c1ccccc1
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
HCl
C(Cl)Cl
100
0.5
COc1ccccc1Cl.O=C(Cl)CCCl>C(Cl)Cl>COc1cc2c(cc1Cl)C(=O)CC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-450375708e3e4b9e984a1b52160e2f1e
CCOC(=O)C#N.COc1cc2c(cc1Cl)C(=O)CC2>>CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O
C(#N)C(=O)OCC.ClC1=C(C=C2CCC(C2=C1)=O)OC.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>>ClC1=C(C=C2CC(C(C2=C1)=O)C(=O)OCC)OC
N#C[C:4]([O:3][CH2:2][CH3:1])=[O:5].[CH2:6]1[CH2:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[c:13]([Cl:14])[cH:15][c:16]2[C:17]1=[O:18]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[c:13]([Cl:14])[cH:15][c:16]2[C:17]1=[O:18]
CCOC(=O)C#N.COc1cc2c(cc1Cl)C(=O)CC2
CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O
null
null
C1CCOC1
C-C Coupling
OtherReaction
0f8301238f55311e0fc642450d793fb0499dfa9b94fae7471e9160ef412b7dd2
ea62efa90ef3cfb13125a23e62e9e1787aa2a0b0ee48c8a61b3326a3bda24134
O=C1CCc2ccccc21
N#C-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].[O;D1;H0:5]=[C:6]1-[CH2;D2;+0:7]-[C:8]-[c:9]:[c:10]-1>>[C:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH;D3;+0:7]1-[C:8]-[c:9]:[c:10]-[C:6]-1=[O;D1;H0:5]
null
[]
-78
CELSIUS
null
null
To a solution of 6-chloro-5-methoxyindan-1-one (27.6 g, 141 mmol) in THF (630 mL) at −78° C. was added a 1.0M solution of lithium bis(trimethylsilyl)amide in THF (309 mL, 309 mmol) and then the solution was slowly warmed to ca −50° C. during 1 hour. After re-cooling to −78° C., ethyl cyanoformate (21.3 mL, 216 mmol) wa...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Nitrile
Ketone.Ester
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
Other
C1CCOC1
-78
null
CCOC(=O)C#N.COc1cc2c(cc1Cl)C(=O)CC2>C1CCOC1>CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-92195910957b4b4d927968fab15171cd
CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O.FCCBr>>COc1cc2c(cc1Cl)C(=O)C(CCF)C2
[OH-].[Na+].ClC1=C(C=C2CC(C(C2=C1)=O)C(=O)OCC)OC.C(=O)([O-])[O-].[K+].[K+].BrCCF>>ClC1=C(C=C2CC(C(C2=C1)=O)CCF)OC
CCOC(=O)[CH:12]1[C:10](=[O:11])[c:6]2[c:5]([cH:4][c:3]([O:2][CH3:1])[c:8]([Cl:9])[cH:7]2)[CH2:16]1.Br[CH2:13][CH2:14][F:15]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([cH:7][c:8]1[Cl:9])[C:10](=[O:11])[CH:12]([CH2:13][CH2:14][F:15])[CH2:16]2
CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O.FCCBr
COc1cc2c(cc1Cl)C(=O)C(CCF)C2
null
null
O.CC(=O)N(C)C
C-C Coupling
OtherReaction
eaf2c6345598db4bafc43dfd5960e2c4d5dab87b5f467fecb90ec97d72862f5e
ce7b75becdbf06d1618bfce7bcc7e9c53441b0656e1b7c7325fe306df5895906
O=C1CCc2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[F;D1;H0:3].C-C-O-C(=O)-[CH;D3;+0:4]1-[C:5]-[c:6]:[c:7]-[C:8]-1=[O;D1;H0:9]>>[F;D1;H0:3]-[C:2]-[CH2;D2;+0:1]-[CH;D3;+0:4]1-[C:5]-[c:6]:[c:7]-[C:8]-1=[O;D1;H0:9]
null
[]
65
CELSIUS
2
HOUR
To a solution of ethyl 6-chloro-5-methoxy-1-oxoindane-2-carboxylate (crude product from the preceding step, ˜141 mmol) in anhydrous dimethylacetamide (540 mL) was added K2CO3 (39 g, 282 mmol), KI (46.8 g, 282 mmol) and 1-bromo-2-fluoroethane (13.5 mL, 183 mmol) and the mixture was stirred and heated at 65° C. for 6 hou...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone.Ester
Ketone
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
HBr
O.CC(=O)N(C)C
65
2
CCOC(=O)C1Cc2cc(OC)c(Cl)cc2C1=O.FCCBr>O.CC(=O)N(C)C>COc1cc2c(cc1Cl)C(=O)C(CCF)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a422c20f5fe84af7b5f05ec4d1685d87
C=CC(C)=O.COc1cc2c(cc1Cl)C(=O)C(CCF)C2>>COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2
[OH-].[K+].C(=C)C(=O)C.ClC1=C(C=C2CC(C(C2=C1)=O)CCF)OC.C=C[C@H]1C[N+]2(CC[C@H]1C[C@@H]2[C@H](C3=CC=NC4=CC=CC=C34)O)CC5=CC=C(C=C5)C(F)(F)F.[Br-]>>ClC1=C(C=C2CC(C(C2=C1)=O)(CCC(C)=O)CCF)OC
[CH2:16]=[CH:17][C:18]([CH3:19])=[O:20].[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([cH:7][c:8]1[Cl:9])[C:10](=[O:11])[CH:12]([CH2:13][CH2:14][F:15])[CH2:21]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([cH:7][c:8]1[Cl:9])[C:10](=[O:11])[C:12]([CH2:13][CH2:14][F:15])([CH2:16][CH2:17][C:18]([CH3:19])=[O:20])[CH2:21]2
C=CC(C)=O.COc1cc2c(cc1Cl)C(=O)C(CCF)C2
COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2
null
null
ClCCl.C1(=CC=CC=C1)C
C-C Coupling
OtherReaction
c504c0d32586144b6874498db3cc99d4d5bb675e1b2e725385a0386d3f14ac05
68a0b2d4768a64505cf15a6dd6bbd75216aef3c50fb86aff9b39341b3e49f06d
O=C1CCc2ccccc21
[C;D1;H3:1]-[C:2](=[O;D1;H0:3])-[CH;D2;+0:4]=[CH2;D1;+0:5].[C:6]-[C:7]-[CH;D3;+0:8]1-[C:9]-[c:10]:[c:11]-[C:12]-1=[O;D1;H0:13]>>[C:6]-[C:7]-[C;H0;D4;+0:8]1(-[CH2;D2;+0:5]-[CH2;D2;+0:4]-[C:2](-[C;D1;H3:1])=[O;D1;H0:3])-[C:9]-[c:10]:[c:11]-[C:12]-1=[O;D1;H0:13]
null
[]
null
null
30
MINUTE
To a solution of 6-chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one (34 g, 140 mmol) in toluene (1500 mL) was added N-[4-(trifluoromethyl)benzyl]cinchoninium bromide (13 g, 24 mmol) and the mixture was stirred at room temperature for 30 minutes. After cooling to 0° C., methyl vinyl ketone (20 mL, 240 mmol) was added follo...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ketone.Vinyl
Ketone.Ketone
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
c1ccc2c(c1)CCC2
null
ClCCl.C1(=CC=CC=C1)C
null
0.5
C=CC(C)=O.COc1cc2c(cc1Cl)C(=O)C(CCF)C2>ClCCl.C1(=CC=CC=C1)C>COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6fc3ff70fc1145e6965aa98f5831f3c5
COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2>>COc1cc2c(cc1Cl)C1=CC(=O)CCC1(CCF)C2
ClC1=C(C=C2CC(C(C2=C1)=O)(CCC(C)=O)CCF)OC.C(C)(=O)O.N1CCCC1>>ClC=1C=C2C3=CC(CCC3(CC2=CC1OC)CCF)=O
O=[C:10]1[c:6]2[c:5]([cH:4][c:3]([O:2][CH3:1])[c:8]([Cl:9])[cH:7]2)[CH2:20][C:16]1([CH2:15][CH2:14][C:12]([CH3:11])=[O:13])[CH2:17][CH2:18][F:19]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([cH:7][c:8]1[Cl:9])[C:10]1=[CH:11][C:12](=[O:13])[CH2:14][CH2:15][C:16]1([CH2:17][CH2:18][F:19])[CH2:20]2
COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2
COc1cc2c(cc1Cl)C1=CC(=O)CCC1(CCF)C2
null
null
C1(=CC=CC=C1)C.CCOC(=O)C
Functional Group Interconversion
OtherReaction
85ff0aa8be631f96366b93c0f2ba199404913ad074e95e1352514ec4827258a9
b7bc018679e3f4c5a72b49c90c858cc3bcb4db12dedb0216b468af50ef8a00a3
O=C1C=C2c3ccccc3CC2CC1
O=[C;H0;D3;+0:1]1-[c:2](:[c:3]):[c:4]-[C:5]-[C:6]-1(-[C:7])-[C:8]-[C:9]-[C:10](-[CH3;D1;+0:11])=[O;D1;H0:12]>>[C:7]-[C:6]12-[C:8]-[C:9]-[C:10](=[O;D1;H0:12])-[CH;D2;+0:11]=[C;H0;D3;+0:1]-1-[c:2](:[c:3]):[c:4]-[C:5]-2
null
[]
95
CELSIUS
null
null
To a solution of 6-chloro-2-(2-fluoroethyl)-5-methoxy-2-(3-oxobutyl)indan-1-one (32 g, 102 mmol) in toluene (1000 mL) were added acetic acid (7.0 mL, 120 mmol) and pyrrolidine (10 mL, 120 mmol) and the solution was heated at 95° C. for 2 hours. After cooling to room temperature, the reaction mixture was diluted with Et...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ketone
Ketone
c1ccc2c(c1)CCC2
C1=C2c3ccccc3CC2CCC1
C1=C2c3ccccc3CC2CCC1
HO-
C1(=CC=CC=C1)C.CCOC(=O)C
95
null
COc1cc2c(cc1Cl)C(=O)C(CCF)(CCC(C)=O)C2>C1(=CC=CC=C1)C.CCOC(=O)C>COc1cc2c(cc1Cl)C1=CC(=O)CCC1(CCF)C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bba0d7e5822746829124c9cba0e9bdee
O=C1C(C(F)(F)F)=C2c3cc(Cl)c4[nH]nnc4c3CC23CCC1C3>>O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3
ClC1=CC=2C=3C4(CC2C=2N=NNC21)CCC(C(C3C(F)(F)F)=O)C4>>FC(C=1C(C2CCC3(C1C=1C=CC4=C(N=NN4)C1C3)C2)=O)(F)F
Cl[c:11]1[cH:10][c:9]2[c:17]([c:16]3[c:12]1[nH:13][n:14][n:15]3)[CH2:18][C:19]13[C:8]2=[C:3]([C:4]([F:5])([F:6])[F:7])[C:2](=[O:1])[CH:22]([CH2:21][CH2:20]1)[CH2:23]3>>[O:1]=[C:2]1[C:3]([C:4]([F:5])([F:6])[F:7])=[C:8]2[c:9]3[cH:10][cH:11][c:12]4[nH:13][n:14][n:15][c:16]4[c:17]3[CH2:18][C:19]23[CH2:20][CH2:21][CH:22]1[C...
O=C1C(C(F)(F)F)=C2c3cc(Cl)c4[nH]nnc4c3CC23CCC1C3
O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3
null
[OH-].[OH-].[Pd+2].[Pd].[OH-].[OH-].[Pd+2].[Pd]
ClCCl.CN(C)C=O
Functional Group Interconversion
Aromatic dehalogenation
9e3085e60c60726e4eccbf2b3b9bcf4e8944c9db2a05e9b4833fce06217a9387
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
O=C1C=C2c3ccc4[nH]nnc4c3CC23CCC1C3
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]:[c:5]2:[#7;a:6]:[#7;a:7]:[#7;a:8]:[c:9]:2:1)-[C:10]=[C:11]>>[C:11]=[C:10]-[c:3]1:[c:2]:[cH;D2;+0:1]:[c:9]2:[#7;a:8]:[#7;a:7]:[#7;a:6]:[c:5]:2:[c:4]:1
null
[]
null
null
29
HOUR
To a solution of 4-chloro-6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta-[1,2]indeno[4,5-d][1,2,3]triazol-7(8H)-one (2.3 g, crude product from the preceding step, ˜6.1 mmol) in DMF (230 mL) were added 20% Pd(OH)2 on carbon (1 g) and 5% palladium on calcium carbonate (1 g) and the mixture was hydrogena...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
C1=C2c3ccc4[nH]nnc4c3CC23CCC(C1)C3
C1=C2c3ccc4[nH]nnc4c3CC23CCC(C1)C3
C1=C2c3ccc4[nH]nnc4c3CC23CCC(C1)C3
Other
[OH-].[OH-].[Pd+2].[Pd].[OH-].[OH-].[Pd+2].[Pd].ClCCl.CN(C)C=O
null
29
O=C1C(C(F)(F)F)=C2c3cc(Cl)c4[nH]nnc4c3CC23CCC1C3>[OH-].[OH-].[Pd+2].[Pd].[OH-].[OH-].[Pd+2].[Pd].ClCCl.CN(C)C=O>O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ee17a8ee917b4310acf2748350a329c2
O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3>>O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3C[C@@]23CC[C@@H]1C3
FC(C=1C(C2CCC3(C1C=1C=CC4=C(N=NN4)C1C3)C2)=O)(F)F>>FC(C=1C([C@@H]2CC[C@]3(C1C=1C=CC4=C(N=NN4)C1C3)C2)=O)(F)F
[O:1]=[C:2]1[C:3]([C:4]([F:5])([F:6])[F:7])=[C:8]2[c:9]3[cH:10][cH:11][c:12]4[nH:13][n:14][n:15][c:16]4[c:17]3[CH2:18][C:19]23[CH2:20][CH2:21][CH:22]1[CH2:23]3>>[O:1]=[C:2]1[C:3]([C:4]([F:5])([F:6])[F:7])=[C:8]2[c:9]3[cH:10][cH:11][c:12]4[nH:13][n:14][n:15][c:16]4[c:17]3[CH2:18][C@@:19]23[CH2:20][CH2:21][C@@H:22]1[CH2:...
O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3
O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3C[C@@]23CC[C@@H]1C3
null
null
C(C)O.CO
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C1C=C2c3ccc4[nH]nnc4c3C[C@@]23CC[C@@H]1C3
null
null
[]
null
null
null
null
6-(trifluoromethyl)-3,9,10,11-tetrahydro-8,10a-methanocyclohepta-[1,2]indeno[4,5-d][1,2,3]triazol-7(8H)-one [1.8 g, (8R,10aS): (8S,10aR) enantiomeric ratio ˜2:1] was dissolved in 1/1 ethanol/methanol (130 mL) and resolved by chiral HPLC on a 2.0×25 cm Daicel Chiralcel OJ column (4 mL injections, elution with 35% EtOH:H...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
C1=C2c3ccc4[nH]nnc4c3C[C@@]23CC[C@@H](C1)C3
null
C(C)O.CO
null
null
O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3CC23CCC1C3>C(C)O.CO>O=C1C(C(F)(F)F)=C2c3ccc4[nH]nnc4c3C[C@@]23CC[C@@H]1C3
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8c6a5076affd492bb306e26b8339b3a6
CSCCO.O=C(O)CCl>>CSCCOCC(=O)O
CSCCO.[H-].[Na+].ClCC(=O)O.Cl.[Cl-].[Na+]>>CSCCOCC(=O)O
[CH3:1][S:2][CH2:3][CH2:4][OH:5].Cl[CH2:6][C:7](=[O:8])[OH:9]>>[CH3:1][S:2][CH2:3][CH2:4][O:5][CH2:6][C:7](=[O:8])[OH:9]
CSCCO.O=C(O)CCl
CSCCOCC(=O)O
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
dd3f9c60e1f90d961a7c01d970ae213561355ee1451f276a3b04696e4b6fae5c
46a6e883cf919b4006e69abfdfd883f458f55c08b3200960c6a5b57c4139fbca
null
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[O;D1;H1:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[O;D1;H1:4]
69.5
[{"value": 69.0, "product": "CSCCOCC(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.5, "product": "CSCCOCC(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 2-methylthioethanol (10.0 g, 0.108 mol) in dry tetrahydrofuran (25 ml) was added dropwise, over 30 min, to a suspension of sodium hydride (9.54 g of a 60% dispersion in mineral oil, 0.238 mol, washed twice with hexane) in dry tetrahydrofuran (250 ml) at 22° C. After 30 min, a solution of chloroacetic acid...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary alcohol
Ether
null
null
null
HCl
O1CCCC1
null
0.5
CSCCO.O=C(O)CCl>O1CCCC1>CSCCOCC(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ecbd4d63304a4295a8e3af1f88159dc3
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOCC(=N)N>>CCOC(=O)c1nc(COCCSC)[nH]c(=O)c1OCc1ccccc1
C(C(=O)OCC)(=O)OCC.C(C1=CC=CC=C1)OCC(=O)OCC.[H-].[Na+].Cl.CSCCOCC(=N)N.[O-]CC.[Na+]>>C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)COCCSC)C(=O)OCC
CCO[C:6](=O)[C:4]([O:3][CH2:2][CH3:1])=[O:5].CCO[C:16](=[O:17])[CH2:18][O:19][CH2:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1.[NH2:7][C:8]([CH2:9][O:10][CH2:11][CH2:12][S:13][CH3:14])=[NH:15]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]([CH2:9][O:10][CH2:11][CH2:12][S:13][CH3:14])[nH:15][c:16](=[O:17])[c:18]1[O...
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOCC(=N)N
CCOC(=O)c1nc(COCCSC)[nH]c(=O)c1OCc1ccccc1
null
null
O1CCCC1.C(C)(=O)O.C(C)O
Aromatic Heterocycle Formation
OtherReaction
46371e328b8a1712f756c7bcf70de676b2e5cf18d81f22c713bd44fafb3129e2
ea76cf999399ad97517ace00236aa5bf5d606c07e4032211096f3bda6a8ec4ae
O=c1[nH]cncc1OCc1ccccc1
C-C-O-[C;H0;D3;+0:1](=O)-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-C-O-[C;H0;D3;+0:6](=[O;D1;H0:7])-[CH2;D2;+0:8]-[#8:9]-[C:10].[#8:11]-[C:12]-[C;H0;D3;+0:13](-[NH2;D1;+0:14])=[NH;D1;+0:15]>>[#8:11]-[C:12]-[c;H0;D3;+0:13]1:[n;H0;D2;+0:14]:[c;H0;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5]):[c;H0;D3;+0:8](-[#8:9]-[C:10]):[c;H0;D...
10.1
[{"value": 10.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)COCCSC)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 10.1, "product": "C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)COCCSC)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
22
CELSIUS
18
HOUR
Diethyl oxalate (2.77 g, 19.0 mmol) and ethyl benzyloxyacetate (3.69 g, 19.0 mmol) in dry tetrahydrofuran (30 ml) were treated at 22° C. with sodium hydride (0.83 g of a 60% dispersion in mineral oil, 20.9 mmol) followed by ethanol (10 μl) and the resulting mixture was stirred at 22° C. for 18 h. The tetrahydrofuran wa...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Ester.Ether.Primary amine
Ester.Ether
null
c1cncnc1
c1cncnc1.c1ccccc1
HO-
O1CCCC1.C(C)(=O)O.C(C)O
22
18
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOCC(=N)N>O1CCCC1.C(C)(=O)O.C(C)O>CCOC(=O)c1nc(COCCSC)[nH]c(=O)c1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a9e2ff3243384a1da476218e33659040
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2>>O=C(O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2
Cl.C(C)(=O)OCC.C(C1=CC=CC=C1)OC1=C(N=C2COCCN2C1=O)C(=O)OCC.[OH-].[Na+]>>C(C1=CC=CC=C1)OC1=C(N=C2COCCN2C1=O)C(=O)O
CC[O:3][C:2](=[O:1])[c:4]1[n:5][c:6]2[n:7]([c:8](=[O:9])[c:10]1[O:11][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH2:19][CH2:20][O:21][CH2:22]2>>[O:1]=[C:2]([OH:3])[c:4]1[n:5][c:6]2[n:7]([c:8](=[O:9])[c:10]1[O:11][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH2:19][CH2:20][O:21][CH2:22]2
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2
O=C(O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2
null
null
C(C)O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1c(OCc2ccccc2)cnc2n1CCOC2
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
96
[{"value": 96.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2COCCN2C1=O)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
25
CELSIUS
30
MINUTE
A solution of intermediate 6, ethyl 3-(benzyloxy)-4-oxo-4,6,7,9-tetrahydropyrimido[2, 1-c][1,4]oxazine-2-carboxylate (0.300 g, 0.91 mmol) in ethanol (10 ml) was treated with 3 ml (3.0 mmol) of 1 N sodium hydroxide and stirred at 25° C. for 30 min. The solution was then acidified with 1 N hydrochloric acid, extracted wi...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1cnc2n(c1)CCOC2
Other
C(C)O
25
0.5
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2>C(C)O>O=C(O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-882afcb75c084747b453be8718594113
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2>>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2
[H][H].C(C1=CC=CC=C1)OC1=C(N=C2COCCN2C1=O)C(=O)OCC>>OC1=C(N=C2COCCN2C1=O)C(=O)OCC
c1ccc(C[O:13][c:12]2[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[n:7][c:8]3[n:9]([c:10]2=[O:11])[CH2:14][CH2:15][O:16][CH2:17]3)cc1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[OH:13])[CH2:14][CH2:15][O:16][CH2:17]2
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2
CCOC(=O)c1nc2n(c(=O)c1O)CCOC2
null
[Pd]
C(C)(=O)OCC.C(C)O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=c1ccnc2n1CCOC2
[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7](:[c:8](=[O;D1;H0:9]):[c:10]:1-[O;H0;D2;+0:11]-C-c1:c:c:c:c:c:1)-[C:12]>>[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7](:[c:8](=[O;D1;H0:9]):[c:10]:1-[OH;D1;+0:11])-[C:12]
94
[{"value": 94.0, "product": "OC1=C(N=C2COCCN2C1=O)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.3, "product": "OC1=C(N=C2COCCN2C1=O)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of intermediate 6, ethyl 3-benzyloxy-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (0.236 g, 0.714 mmol) in a mixture of ethyl acetate (60 ml) and ethanol (20 ml) was treated with 1 atm of hydrogen at 25° C. over 10% palladium on activated carbon (0.10 g) for 2.5 h to give 0.160 g (94% y...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1cnc2n(c1)CCOC2
Other
[Pd].C(C)(=O)OCC.C(C)O
null
null
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2>[Pd].C(C)(=O)OCC.C(C)O>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fc1b33f1b3d544009377fcc2ac6b142b
CC(Br)C(=O)O.CSCCO>>CSCCOC(C)C(=O)O
CSCCO.[H-].[Na+].BrC(C(=O)O)C>>CSCCOC(C(=O)O)C
Br[CH:6]([CH3:7])[C:8](=[O:9])[OH:10].[CH3:1][S:2][CH2:3][CH2:4][OH:5]>>[CH3:1][S:2][CH2:3][CH2:4][O:5][CH:6]([CH3:7])[C:8](=[O:9])[OH:10]
CC(Br)C(=O)O.CSCCO
CSCCOC(C)C(=O)O
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
fda3169c328a6f91cb846e38fa3ac4b3ce257430d2fcd0b686a69a7f68177524
94d87fb4ea980bbbd72819243a58e7529341c8cedb8a1df6d3eb0aee97042951
null
Br-[CH;D3;+0:1](-[C;D1;H3:2])-[C:3](=[O;D1;H0:4])-[O;D1;H1:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[CH;D3;+0:1](-[C;D1;H3:2])-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]
78
[{"value": 78.0, "product": "CSCCOC(C(=O)O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.9, "product": "CSCCOC(C(=O)O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Addition of 2-methylthioethanol (10.0 g, 0.108 mol) to sodium hydride (9.54 g of a 60% dispersion in mineral oil, 0.238 mol, washed twice with hexane) followed by reaction with 2-bromopropionic acid (16.6 g, 0.108 mol) gave 13.81 g (78% yield) of the title compound as a clear oil; bp 80-90° C./0.2 torr (bulb to bulb di...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Primary alcohol
Ether
null
null
null
HBr
null
null
null
CC(Br)C(=O)O.CSCCO>>CSCCOC(C)C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8e961f4262fe4f58bd3081ac9c1db85e
CSCCOC(C)C(=O)O>>COC(=O)C(C)OCCSC
CSCCOC(C(=O)O)C.C(C(=O)Cl)(=O)Cl>>CSCCOC(C(=O)OC)C
[OH:2][C:3](=[O:4])[CH:5]([CH3:6])[O:7][CH2:8][CH2:9][S:10][CH3:11]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH3:6])[O:7][CH2:8][CH2:9][S:10][CH3:11]
CSCCOC(C)C(=O)O
COC(=O)C(C)OCCSC
null
null
CO
Miscellaneous
Protection of carboxylic acid
56520e0abb4535dce9a663824ca803b71c2c0dd72dfd246317d953596a987bd2
2ccc7a30191c2c171b49e8a0217bee87430687dd0f567141eca025a75b7e3136
null
[C:1]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:4]>>[C:1]-[C:2](=[O;D1;H0:3])-[O;H0;D2;+0:4]-[C;D1;H3:5]
96
[{"value": 96.0, "product": "CSCCOC(C(=O)OC)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Reaction of intermediate 9, 2-(2-(methylthio)ethoxy)propanoic acid, (13.70 g, 0.083 mol) with oxalyl chloride followed by reaction with methanol gave 14.27 g (96% yield) of the title ester as a clear oil; bp 55-60° C./0.3 torr (bulb to bulb distillation, air bath temperature). 1HNMR 400 MHz (CDCl3) δ ppm: 1.42 (3H, d, ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Ester
null
null
null
Other
CO
null
null
CSCCOC(C)C(=O)O>CO>COC(=O)C(C)OCCSC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-609db6aad0224a97bf8b94d9ef29a8ca
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOC(C)C(=N)N>>CCOC(=O)c1nc(C(C)OCCSC)[nH]c(=O)c1OCc1ccccc1
C(C(=O)OCC)(=O)OCC.C(C1=CC=CC=C1)OCC(=O)OCC.[H-].[Na+].Cl.CSCCOC(C(=N)N)C.[O-]CC.[Na+]>>C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)C(C)OCCSC)C(=O)OCC
CCO[C:6](=O)[C:4]([O:3][CH2:2][CH3:1])=[O:5].CCO[C:17](=[O:18])[CH2:19][O:20][CH2:21][c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1.[NH2:7][C:8]([CH:9]([CH3:10])[O:11][CH2:12][CH2:13][S:14][CH3:15])=[NH:16]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]([CH:9]([CH3:10])[O:11][CH2:12][CH2:13][S:14][CH3:15])[nH:16][c:17]...
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOC(C)C(=N)N
CCOC(=O)c1nc(C(C)OCCSC)[nH]c(=O)c1OCc1ccccc1
null
null
O1CCCC1.C(C)O
Aromatic Heterocycle Formation
OtherReaction
46371e328b8a1712f756c7bcf70de676b2e5cf18d81f22c713bd44fafb3129e2
ea76cf999399ad97517ace00236aa5bf5d606c07e4032211096f3bda6a8ec4ae
O=c1[nH]cncc1OCc1ccccc1
C-C-O-[C;H0;D3;+0:1](=O)-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-C-O-[C;H0;D3;+0:6](=[O;D1;H0:7])-[CH2;D2;+0:8]-[#8:9]-[C:10].[#8:11]-[C:12](-[C;D1;H3:13])-[C;H0;D3;+0:14](-[NH2;D1;+0:15])=[NH;D1;+0:16]>>[#8:11]-[C:12](-[C;D1;H3:13])-[c;H0;D3;+0:14]1:[n;H0;D2;+0:15]:[c;H0;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5]):[c;H0;D3...
15.1
[{"value": 15.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)C(C)OCCSC)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 15.1, "product": "C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)C(C)OCCSC)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Diethyl oxalate (5.66 g, 38.7 mmol) and ethyl benzyloxyacetate (7.52 g, 38.7 mmol) in dry tetrahydrofuran (60 ml) were treated at 22° C. with sodium hydride (1.70 g of a 60% dispersion in mineral oil, 42.5 mmol) and the condensation product was reacted with a mixture of intermediate 11, 2-(2-(methylthio)ethoxy)propanam...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Ester.Ether.Primary amine
Ester.Ether
null
c1cncnc1
c1cncnc1.c1ccccc1
HO-
O1CCCC1.C(C)O
null
null
CCOC(=O)C(=O)OCC.CCOC(=O)COCc1ccccc1.CSCCOC(C)C(=N)N>O1CCCC1.C(C)O>CCOC(=O)c1nc(C(C)OCCSC)[nH]c(=O)c1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f49ea71d7161479a8a4f4fd180901276
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C>>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2C
C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)C)C(=O)OCC.[H][H]>>OC1=C(N=C2C(OCCN2C1=O)C)C(=O)OCC
c1ccc(C[O:13][c:12]2[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[n:7][c:8]3[n:9]([c:10]2=[O:11])[CH2:14][CH2:15][O:16][CH:17]3[CH3:18])cc1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[OH:13])[CH2:14][CH2:15][O:16][CH:17]2[CH3:18]
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C
CCOC(=O)c1nc2n(c(=O)c1O)CCOC2C
null
[Pd]
C(C)(=O)OCC.C(C)O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=c1ccnc2n1CCOC2
[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7](:[c:8](=[O;D1;H0:9]):[c:10]:1-[O;H0;D2;+0:11]-C-c1:c:c:c:c:c:1)-[C:12]>>[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7](:[c:8](=[O;D1;H0:9]):[c:10]:1-[OH;D1;+0:11])-[C:12]
95.6
[{"value": 95.0, "product": "OC1=C(N=C2C(OCCN2C1=O)C)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.6, "product": "OC1=C(N=C2C(OCCN2C1=O)C)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Hydrogenolysis of intermediate 14, ethyl 3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (0.610 g, 1.77 mmol) in a mixture of ethyl acetate (75 ml) and ethanol (75 ml) at 25° C. over 10% palladium on activated carbon (0.20 g) under 1 atm of hydrogen for 2 h gave 0.430 g (95% yiel...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1cnc2n(c1)CCO[CH]2
Other
[Pd].C(C)(=O)OCC.C(C)O
null
null
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C>[Pd].C(C)(=O)OCC.C(C)O>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-110553af96dd488c97415d9811a0c00b
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C>>CC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)C)C(=O)OCC>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)C)C(=O)O
CC[O:12][C:10]([c:9]1[n:8][c:7]2[n:6]([c:22](=[O:23])[c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1)[CH2:5][CH2:4][O:3][CH:2]2[CH3:1])=[O:11]>>[CH3:1][CH:2]1[O:3][CH2:4][CH2:5][n:6]2[c:7]1[n:8][c:9]([C:10](=[O:11])[OH:12])[c:13]([O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1)[c:22]2=[O:23]
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C
CC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
null
null
C(C)(=O)OCC.CCCCCC
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1c(OCc2ccccc2)cnc2n1CCOC2
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
96
[{"value": 96.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)C)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Saponification of intermediate 14, ethyl 3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (0.225 g, 0.65 mmol) as described in the preparation of intermediate 7 gave 0.198 g (96% yield) of the title acid as white crystals; mp 167-168° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cnc2n(c1)CCO[CH]2.c1ccccc1
Other
C(C)(=O)OCC.CCCCCC
null
null
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C>C(C)(=O)OCC.CCCCCC>CC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9a6cfdad163f4f679e5626af00745182
CSCCC=O.OCCO>>CSCCC1OCCO1
CSCCC=O.C(CO)O.C1(=CC=C(C=C1)S(=O)(=O)O)C>>CSCCC1OCCO1
[CH3:1][S:2][CH2:3][CH2:4][CH:5]=[O:6].O[CH2:7][CH2:8][OH:9]>>[CH3:1][S:2][CH2:3][CH2:4][CH:5]1[O:6][CH2:7][CH2:8][O:9]1
CSCCC=O.OCCO
CSCCC1OCCO1
null
null
C1=CC=CC=C1
Heteroatom Alkylation and Arylation
OtherReaction
fe0fbb45a87f24c1e456c6b4e41101562cd8f0af3ec376bb6115e7c1555d997b
7ac65b5a5f576337ce8e86e0130eb9b4757ca21b2419a0e82bbdfd5def30ee73
C1COCO1
O-[CH2;D2;+0:1]-[C:2]-[OH;D1;+0:3].[C:4]-[C:5]-[CH;D2;+0:6]=[O;H0;D1;+0:7]>>[C:4]-[C:5]-[CH;D3;+0:6]1-[O;H0;D2;+0:7]-[CH2;D2;+0:1]-[C:2]-[O;H0;D2;+0:3]-1
null
[]
null
null
null
null
A solution of 3-(methylthio)propanal (5.2 g, 0.05 mol) and ethyleneglycol (3.4g. 0.055 mol) in 100 mL of benzene was treated with 300 mg p-toluenesulfonic acid and heated at reflux for 4 hrs. The solution was cooled and decanted. Concentration and drying in vacuo provided the title compound as a light yellow oil. 1H NM...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary alcohol.Primary alcohol
Ether.Ether
null
C1COCO1
C1COCO1
HO-
C1=CC=CC=C1
null
null
CSCCC=O.OCCO>C1=CC=CC=C1>CSCCC1OCCO1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1dd8fca67b874a688e2ad49b85dbc1d1
CSCCC(C#N)OCCO[Si](C)(C)C.N>>CSCCC(OCCO[Si](C)(C)C)C(=N)N
CSCCC(C#N)OCCO[Si](C)(C)C.N>>CSCCC(C(=N)N)OCCO[Si](C)(C)C
[CH3:1][S:2][CH2:3][CH2:4][CH:5]([O:6][CH2:7][CH2:8][O:9][Si:10]([CH3:11])([CH3:12])[CH3:13])[C:14]#[N:15].[NH3:16]>>[CH3:1][S:2][CH2:3][CH2:4][CH:5]([O:6][CH2:7][CH2:8][O:9][Si:10]([CH3:11])([CH3:12])[CH3:13])[C:14](=[NH:15])[NH2:16]
CSCCC(C#N)OCCO[Si](C)(C)C.N
CSCCC(OCCO[Si](C)(C)C)C(=N)N
null
null
CO
Heteroatom Alkylation and Arylation
OtherReaction
080bc392517146a8e4e2652444810e882b6d922fa0c927a2aa6ffbd2ba45a361
807c02e8854fa1d85bad1ac2ebd73d5cdddf0728c08cb10c1d1278b952c720d7
null
[#8:1]-[C:2](-[C:3])-[C;H0;D2;+0:4]#[N;H0;D1;+0:5].[NH3;D0;+0:6]>>[#8:1]-[C:2](-[C:3])-[C;H0;D3;+0:4](-[NH2;D1;+0:6])=[NH;D1;+0:5]
null
[]
85
CELSIUS
null
null
A solution of intermediate 18, 4-(methylthio)-2-(2-(trimethylsilyloxy)ethoxy)butanenitrile, (4.9 g, 0.02 mol) in 30 mL of methanol was saturated with ammonia. The flask was then sealed and heated in an oil bath at 80-90° C. for 16 hrs. After cooling, the flask was opened and the mixture concentrated in vacuo to give th...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
null
null
CO
85
null
CSCCC(C#N)OCCO[Si](C)(C)C.N>CO>CSCCC(OCCO[Si](C)(C)C)C(=N)N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0056a5d036354ceb9d834db32c6ae8e5
CCOC(=O)c1nc(C(CCSC)OCCO)[nH]c(=O)c1OCc1ccccc1>>CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC
CSOC(=O)I.C(C1=CC=CC=C1)OC1=C(N=C(NC1=O)C(CCSC)OCCO)C(=O)OCC.CCN(CC)CC>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)OCC
O[CH2:21][CH2:22][O:23][CH:24]([c:8]1[n:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:12]([O:13][CH2:14][c:15]2[cH:16][cH:17][cH:18][cH:19][cH:20]2)[c:10](=[O:11])[nH:9]1)[CH2:25][CH2:26][S:27][CH3:28]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[O:13][CH2:14][c:15]1[cH:16][cH:17][cH:18]...
CCOC(=O)c1nc(C(CCSC)OCCO)[nH]c(=O)c1OCc1ccccc1
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC
null
null
CCOCC.C(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
3d4dd7481546b89bdfc13d988499cecab9925696be00935421ee0a9674a0a7e2
2ab4024aa17b6e89368e6fe8ee731d32c7611cb9b23de403e301e8362fea90b1
O=c1c(OCc2ccccc2)cnc2n1CCOC2
O-[CH2;D2;+0:1]-[C:2]-[#8:3]-[C:4]-[c:5]1:[#7;a:6]:[c:7](-[C:8](-[#8:9])=[O;D1;H0:10]):[c:11]:[c:12](=[O;D1;H0:13]):[nH;D2;+0:14]:1>>[#8:9]-[C:8](=[O;D1;H0:10])-[c:7]1:[#7;a:6]:[c:5]2:[n;H0;D3;+0:14](:[c:12](=[O;D1;H0:13]):[c:11]:1)-[CH2;D2;+0:1]-[C:2]-[#8:3]-[C:4]-2
52.4
[{"value": 52.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.4, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
To a solution of intermediate 20, ethyl 5-(benzyloxy)-2-(1-(2-hydroxyethoxy)-3-(methylthio)propyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate, (527 mg, 1.25 mmol) and Et3N (505 mg, 5 mmol) dissolved in 10 mL of CH2Cl2 was added a solution of CH3SO2CI (288 mg, 2.5 mmol) dissolved in 2 mL of CH2Cl2. This was stirred for 2...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
null
c1cncnc1
c1cnc2n(c1)CCO[CH]2
c1ccccc1.c1cnc2n(c1)CCO[CH]2
HO-
CCOCC.C(Cl)Cl
null
20
CCOC(=O)c1nc(C(CCSC)OCCO)[nH]c(=O)c1OCc1ccccc1>CCOCC.C(Cl)Cl>CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5291017c03be47b0ae782e7a8b38a8ce
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC>>CSCCC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
Cl.C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)OCC.[OH-].[Li+]>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)O
CC[O:15][C:13]([c:12]1[n:11][c:10]2[n:9]([c:25](=[O:26])[c:16]1[O:17][CH2:18][c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1)[CH2:8][CH2:7][O:6][CH:5]2[CH2:4][CH2:3][S:2][CH3:1])=[O:14]>>[CH3:1][S:2][CH2:3][CH2:4][CH:5]1[O:6][CH2:7][CH2:8][n:9]2[c:10]1[n:11][c:12]([C:13](=[O:14])[OH:15])[c:16]([O:17][CH2:18][c:19]1[cH:20][...
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC
CSCCC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
null
null
O1CCCC1.O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1c(OCc2ccccc2)cnc2n1CCOC2
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
108.9
[{"value": 88.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 108.9, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)CCSC)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a stirred solution of intermediate 21, ethyl 3-(benzyloxy)-9-(2-(methylthio)ethyl)-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate (97 mg, 0.2mmol) in 3 mL tetrahydrofuran was added lithium hydroxide (1 5 mg, 0.6 mmol) in 3 mL water. After 20 min the reaction mixture was acidified with 1N HCl and e...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cnc2n(c1)CCO[CH]2.c1ccccc1
Other
O1CCCC1.O
null
null
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2CCSC>O1CCCC1.O>CSCCC1OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-124c1e87c7ed41acb94650cfba9e2194
CC(C)(O)C#N.OCCCl>>CC(C)(C#N)OCCCl
CC(C#N)(O)C.ClCCO>>ClCCOC(C#N)(C)C
O[C:2]([CH3:1])([CH3:3])[C:4]#[N:5].[OH:6][CH2:7][CH2:8][Cl:9]>>[CH3:1][C:2]([CH3:3])([C:4]#[N:5])[O:6][CH2:7][CH2:8][Cl:9]
CC(C)(O)C#N.OCCCl
CC(C)(C#N)OCCCl
null
[Cl-].[Cl-].[Zn+2]
O
Heteroatom Alkylation and Arylation
Alcohol to ether
684823df159a4c07d0a2a3c5a4e8843a8449fd560dd00a2ccbb32e95f87ee6bc
71d6b370ca48f1d75269bb2a372b1608a88e28617e379e11884cc0e510f32096
null
O-[C;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-[C:4]#[N;D1;H0:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-[C:4]#[N;D1;H0:5]
63.8
[{"value": 63.8, "product": "ClCCOC(C#N)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.8, "product": "ClCCOC(C#N)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
19
HOUR
(Navalokina, R. Et al J. Org. Chem. USSR (Engl. Trans.), 1980, 16, 1382-1386. 2) Ramalingam, K. U.S. Pat. No. 4,864,051, 1989.). A 250 mL round bottom flask was charged with ZnCl2 (68.14 g, 0.5 mole) which was then fused by heating under vacuum. After returning to room temperature the material was placed under an atmos...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Tertiary alcohol
Ether
null
null
null
HO-
[Cl-].[Cl-].[Zn+2].O
60
19
CC(C)(O)C#N.OCCCl>[Cl-].[Cl-].[Zn+2].O>CC(C)(C#N)OCCCl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4f89fd02f88441029ad2c55e62c0b6f5
CC(C)(C#N)OCCCl.CCOC(=O)C#CC(=O)OCC.NO>>CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1
ClCCOC(C#N)(C)C.[Na+].[I-].NO.C(#CC(=O)OCC)C(=O)OCC>>C(C)OC(CC1(N=C2C(OCCN2O1)(C)C)C(=O)OCC)=O
Cl[CH2:16][CH2:17][O:18][C:19]([C:14]#[N:13])([CH3:20])[CH3:21].[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6]#[C:7][C:8](=[O:9])[O:10][CH2:11][CH3:12].[NH2:15][OH:22]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][C:7]1([C:8](=[O:9])[O:10][CH2:11][CH3:12])[N:13]=[C:14]2[N:15]([CH2:16][CH2:17][O:18][C:19]2([CH3:20])[CH3:21])[O:22]1
CC(C)(C#N)OCCCl.CCOC(=O)C#CC(=O)OCC.NO
CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1
null
null
C(C)(=O)OCC.C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
a5917d702028448357f7058ae5e40c87e2d8f4c235ca1dccfb49bd3cb6625926
69880389a496532f744726aac1f0914237c6d43769e736157ffa6a51cc5861a0
C1CN2OCN=C2CO1
Cl-[CH2;D2;+0:1]-[C:2]-[#8:3]-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;H0;D2;+0:7]#[N;H0;D1;+0:8].[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[C;H0;D2;+0:13]#[C;H0;D2;+0:14]-[C:15](=[O;D1;H0:16])-[#8:17]-[C:18].[NH2;D1;+0:19]-[OH;D1;+0:20]>>[C:9]-[#8:10]-[C:11](=[O;D1;H0:12])-[C;H0;D4;+0:13]1(-[CH2;D2;+0:14]-[C:15](=[O;D1;H0:16])-...
48.6
[{"value": 48.6, "product": "C(C)OC(CC1(N=C2C(OCCN2O1)(C)C)C(=O)OCC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.6, "product": "C(C)OC(CC1(N=C2C(OCCN2O1)(C)C)C(=O)OCC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
1
HOUR
To a stirred solution of intermediate 23, 2-(2-chloroethoxy)-2-methylpropanenitrile (14.7 g, 0.10 mole) and NaI (1.5 g, 10 mmol) in ethanol (50 mL) was added an aqueous solution (50%) of hydroxylamine (18.4 g, 0.30 mole) resulting in an exothermic reaction. Following this the reaction mixture was heated at 80° C. for 2...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Ester.Nitrile.Primary amine
Ester.Ester.Tertiary amine
null
C1CN2OCN=C2CO1
C1CN2OCN=C2CO1
HCl
C(C)(=O)OCC.C(C)O
80
1
CC(C)(C#N)OCCCl.CCOC(=O)C#CC(=O)OCC.NO>C(C)(=O)OCC.C(C)O>CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4a1e0766d68d419a8ed9541ae0e65e6a
CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1>>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C
C(C)OC(CC1(N=C2C(OCCN2O1)(C)C)C(=O)OCC)=O.C(C)(=O)OCC>>OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC
CCO[C:10](=[O:11])[CH2:12][C:6]1([C:4]([O:3][CH2:2][CH3:1])=[O:5])[N:7]=[C:8]2[N:9]([O:13]1)[CH2:14][CH2:15][O:16][C:17]2([CH3:18])[CH3:19]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[OH:13])[CH2:14][CH2:15][O:16][C:17]2([CH3:18])[CH3:19]
CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1
CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C
null
null
CC1=C(C=C(C=C1)C)C.CCOCC
Aromatic Heterocycle Formation
OtherReaction
a03f9eaa5e7eb0271a37ed1901b591f530bbce8c6ece25823a3d06c99dead24a
fa33563db5d782f36d1ac7f6cdbda7c5595318d1e5a1cdb5a6a9b112b123a622
O=c1ccnc2n1CCOC2
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:3]-[C;H0;D4;+0:4]1(-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8])-[N;H0;D2;+0:9]=[C;H0;D3;+0:10]2-[N;H0;D3;+0:11](-[C:12]-[C:13]-[#8:14]-[C:15]-2(-[C;D1;H3:16])-[C;D1;H3:17])-[O;H0;D2;+0:18]-1>>[C:8]-[#8:7]-[C:5](=[O;D1;H0:6])-[c;H0;D3;+0:4]1:[n;H0;D2;+0:9]:[c;H0;D3;+0:10]2:[n;H0;D3;+0...
18
[{"value": 18.0, "product": "OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of intermediate 24, ethyl 2-(2-ethoxy-2-oxoethyl)-8,8-dimethyl-2,5,6,8-tetrahydro-[1,2,4]oxadiazolo[3,2-c][1,4]oxazine-2-carboxylate (31.16 g) in 1,2,4-trimethylbenzene (200 mL) was heated at 180° C. for 5 h. The resulting dark reaction solution was cooled then concentrated to give a dark brown paste which w...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester.Tertiary amine
Ester.Aromatic alcohol
C1CN2OCN=C2CO1
C1OCCn2cccnc21
C1OCCn2cccnc21
HO-
CC1=C(C=C(C=C1)C)C.CCOCC
null
null
CCOC(=O)CC1(C(=O)OCC)N=C2N(CCOC2(C)C)O1>CC1=C(C=C(C=C1)C)C.CCOCC>CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-46e52e1d4b404d63aee04a451e7bd9d5
BrCc1ccccc1.CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C>>CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C
OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC.C(C1=CC=CC=C1)Br.C(=O)([O-])[O-].[K+].[K+]>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC
Br[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[OH:13])[CH2:21][CH2:22][O:23][C:24]2([CH3:25])[CH3:26]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[n:7][c:8]2[n:9]([c:10](=[O:11])[c:12]1[O:13][CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20...
BrCc1ccccc1.CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C
null
null
CCOCC.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=c1c(OCc2ccccc2)cnc2n1CCOC2
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#8:5]-[C:6](=[O;D1;H0:7])-[c:8]1:[#7;a:9]:[c:10]:[#7;a:11](:[c:12](=[O;D1;H0:13]):[c:14]:1-[OH;D1;+0:15])-[C:16]>>[#8:5]-[C:6](=[O;D1;H0:7])-[c:8]1:[#7;a:9]:[c:10]:[#7;a:11](:[c:12](=[O;D1;H0:13]):[c:14]:1-[O;H0;D2;+0:15]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[C:16]
78
[{"value": 78.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.8, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
48
HOUR
To a stirred solution of intermediate 25, ethyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (2.68 g, 10 mmol) and benzyl bromide (1.43 mL, 12 mmol) in DMF (40 mL) was added K2CO3 (2.07 g, 20 mmol). After stirring 48 h at ambient temperature, the reaction mixture was diluted...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1OCCn2cccnc21
HBr
CCOCC.CN(C)C=O
null
48
BrCc1ccccc1.CCOC(=O)c1nc2n(c(=O)c1O)CCOC2(C)C>CCOCC.CN(C)C=O>CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-063cc7d486744680af9ee528e8b6a26a
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C>>CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)OCC.O[Li].O>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)O
CC[O:13][C:11]([c:10]1[n:9][c:8]2[n:7]([c:23](=[O:24])[c:14]1[O:15][CH2:16][c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22]1)[CH2:6][CH2:5][O:4][C:2]2([CH3:1])[CH3:3])=[O:12]>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][CH2:6][n:7]2[c:8]1[n:9][c:10]([C:11](=[O:12])[OH:13])[c:14]([O:15][CH2:16][c:17]1[cH:18][cH:19][cH:20][cH:21][cH:22...
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C
CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
null
null
C(C)O.O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1c(OCc2ccccc2)cnc2n1CCOC2
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
99
[{"value": 99.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.9, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCN2C1=O)(C)C)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A mixture of intermediate 26, ethyl 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4] oxazine-2-carboxylate, (2.93 g, 8.2 mmol) and LiOH.H2O (0.84 g, 20 mmol) in 4:1 ethanol/tetrahydrofuran (50 mL) was stirred for 2 h at ambient temperature then concentrated under vacuum. The resulting yellow resi...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1OCCn2cccnc21.c1ccccc1
Other
C(C)O.O1CCCC1
null
2
CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2(C)C>C(C)O.O1CCCC1>CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7e02cac3d14d472a81bae5ec19de709e
CCC(O)(C#N)CC.OCCCl>>CCC(C#N)(CC)OCCCl
C(C)C(C#N)(CC)O.ClCCO>>ClCCOC(C#N)(CC)CC
[CH3:1][CH2:2][C:3]([C:4]#[N:5])([CH2:6][CH3:7])[OH:8].O[CH2:9][CH2:10][Cl:11]>>[CH3:1][CH2:2][C:3]([C:4]#[N:5])([CH2:6][CH3:7])[O:8][CH2:9][CH2:10][Cl:11]
CCC(O)(C#N)CC.OCCCl
CCC(C#N)(CC)OCCCl
null
[Cl-].[Zn+2].[Cl-].[Zn]
O
Heteroatom Alkylation and Arylation
Alcohol to ether
684823df159a4c07d0a2a3c5a4e8843a8449fd560dd00a2ccbb32e95f87ee6bc
71d6b370ca48f1d75269bb2a372b1608a88e28617e379e11884cc0e510f32096
null
O-[CH2;D2;+0:1]-[C:2]-[Cl;D1;H0:3].[C:4]-[C:5](-[C:6])(-[OH;D1;+0:7])-[C:8]#[N;D1;H0:9]>>[C:4]-[C:5](-[C:6])(-[C:8]#[N;D1;H0:9])-[O;H0;D2;+0:7]-[CH2;D2;+0:1]-[C:2]-[Cl;D1;H0:3]
39,471.1
[{"value": 39471.1, "product": "ClCCOC(C#N)(CC)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
20
HOUR
Zinc chloride (68.1 g, 0.5 mol) was fused under vacuum as described in the procedure for the synthesis of intermediate 23. The molten zinc was cooled and the evacuated flask was flushed with nitrogen. The flask was loaded with intermediate 28, 2-ethyl-2-hydroxybutanenitrile, (40.3 g, 0.5 mol) and 2-chloroethanol (50.5 ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Tertiary alcohol
Ether
null
null
null
HO-
[Cl-].[Zn+2].[Cl-].[Zn].O
60
20
CCC(O)(C#N)CC.OCCCl>[Cl-].[Zn+2].[Cl-].[Zn].O>CCC(C#N)(CC)OCCCl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ab0304298cbf48caa8874bbebe443ba8
BrCc1ccccc1.CCOC(=O)c1nc(C(C)(C)OCCCCl)[nH]c(=O)c1O>>CC1(C)OCCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
C(C1=CC=CC=C1)Br.ClCCCOC(C)(C)C=1NC(C(=C(N1)C(=O)OCC)O)=O.C([O-])([O-])=O.[K+].[K+].O>>C(C1=CC=CC=C1)OC1=C(N=C2C(OCCCN2C1=O)(C)C)C(=O)O
Br[CH2:17][c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1.CC[O:14][C:12]([c:11]1[n:10][c:9]([C:2]([CH3:1])([CH3:3])[O:4][CH2:5][CH2:6][CH2:7]Cl)[nH:8][c:24](=[O:25])[c:15]1[OH:16])=[O:13]>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][CH2:6][CH2:7][n:8]2[c:9]1[n:10][c:11]([C:12](=[O:13])[OH:14])[c:15]([O:16][CH2:17][c:18]1[cH:19][cH:...
BrCc1ccccc1.CCOC(=O)c1nc(C(C)(C)OCCCCl)[nH]c(=O)c1O
CC1(C)OCCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
de0a20280e677f94ca9d770b04253e74f22df4e7b24d912058580f57db6b1057
623e79ee6d04301e24a593b393382fd53fb40863aab75093f67aae06cd334cb4
O=c1c(OCc2ccccc2)cnc2n1CCCOC2
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].C-C-[O;H0;D2;+0:5]-[C:6](=[O;D1;H0:7])-[c:8]1:[#7;a:9]:[c:10](-[C:11]):[nH;D2;+0:12]:[c:13](=[O;D1;H0:14]):[c:15]:1-[OH;D1;+0:16].Cl-[CH2;D2;+0:17]-[C:18]-[C:19]>>[C:11]-[c:10]1:[#7;a:9]:[c:8](-[C:6](=[O;D1;H0:7])-[OH;D1;+0:5]):[c:15](-[O;H0;D2;+0:16]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:...
135.7
[{"value": 100.0, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCCN2C1=O)(C)C)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 135.7, "product": "C(C1=CC=CC=C1)OC1=C(N=C2C(OCCCN2C1=O)(C)C)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
5
HOUR
A suspension of intermediate 33, ethyl 2-(2-(3-chloropropoxy)propan-2-yl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate, (0.205 g, 0.64 mmol) and anhydrous potassium carbonate (0.361 g, 2.6 mmol) in anhydrous dimethylformamide (4 mL) was stirred at 60° C. for 5 hours. The reaction mixture was treated with benzyl ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary halide.Ester.Aromatic alcohol
Carboxylic acid.Ether
c1cncnc1
C1OCCCn2cccnc21
C1OCCCn2cccnc21.c1ccccc1
HCl.Br-
CN(C=O)C
60
5
BrCc1ccccc1.CCOC(=O)c1nc(C(C)(C)OCCCCl)[nH]c(=O)c1O>CN(C=O)C>CC1(C)OCCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-68aee97f0d9f4ec9b2a3d3c7715b29a2
N#Cc1ccc(F)c2ccccc12>>NCc1ccc(F)c2ccccc12
C(#N)C1=CC=C(C2=CC=CC=C12)F.Cl>>Cl.FC1=CC=C(C2=CC=CC=C12)CN
[N:2]#[C:3][c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]12>>[NH2:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]12
N#Cc1ccc(F)c2ccccc12
NCc1ccc(F)c2ccccc12
null
[Pd]
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
c1ccc2ccccc2c1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
44
[{"value": 44.0, "product": "Cl.FC1=CC=C(C2=CC=CC=C12)CN", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 1-cyano-4-fluoronapthalene (1.05 g, 6.12 mmol) and 1.5 mL of HCl (aq.) in absolute ethanol (50 mL) was stirred under a hydrogen atmosphere (balloon) with 10% palladium on carbon (0.20 g) for 16 hours. The catalyst was removed by filtration through Celite, and the filtrate concentrated under vacuum. The re...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccc2ccccc2c1
null
[Pd].C(C)O
null
null
N#Cc1ccc(F)c2ccccc12>[Pd].C(C)O>NCc1ccc(F)c2ccccc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2fb731be3faf44ceab7ee9f2b74b19ef
CNC(=O)c1cc(F)ccc1CNC(=O)OC(C)(C)C>>CNC(=O)c1cc(F)ccc1CN
FC1=CC(=C(CNC(OC(C)(C)C)=O)C=C1)C(NC)=O.C(F)(F)(F)C(=O)O>>FC(C(=O)O)(F)F.NCC1=C(C(=O)NC)C=C(C=C1)F
CC(C)(C)OC(=O)[NH:13][CH2:12][c:11]1[c:5]([C:3]([NH:2][CH3:1])=[O:4])[cH:6][c:7]([F:8])[cH:9][cH:10]1>>[CH3:1][NH:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([F:8])[cH:9][cH:10][c:11]1[CH2:12][NH2:13]
CNC(=O)c1cc(F)ccc1CNC(=O)OC(C)(C)C
CNC(=O)c1cc(F)ccc1CN
null
null
C(Cl)Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[c:3]>>[NH2;D1;+0:1]-[C:2]-[c:3]
99
[{"value": 99.0, "product": "FC(C(=O)O)(F)F.NCC1=C(C(=O)NC)C=C(C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To a solution of tert-butyl 4-fluoro-2-(methylcarbamoyl)benzylcarbamate (7.70 g, 27.3 mmol; prepared from 2-bromo-5-fluorobenzoic acid using literature methods) in CH2Cl2 (100 mL) was added CF3CO2H (25 mL) and the mixture stirred at room temperature for 15 min. This was concentrated in vacuo and the residue triturated ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1
HO-
C(Cl)Cl
null
0.25
CNC(=O)c1cc(F)ccc1CNC(=O)OC(C)(C)C>C(Cl)Cl>CNC(=O)c1cc(F)ccc1CN
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c45a397e4adf4ad7891030fc2fdac556
CC(C)(C)OC(=O)NCc1ccc(F)cc1C(=O)NC1CC1>>NCc1ccc(F)cc1C(=O)NC1CC1
C1(CC1)NC(=O)C1=C(CNC(OC(C)(C)C)=O)C=CC(=C1)F.FC(C(=O)O)(F)F>>FC(C(=O)O)(F)F.NCC1=C(C(=O)NC2CC2)C=C(C=C1)F
CC(C)(C)OC(=O)[NH:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([F:7])[cH:8][c:9]1[C:10](=[O:11])[NH:12][CH:13]1[CH2:14][CH2:15]1>>[NH2:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([F:7])[cH:8][c:9]1[C:10](=[O:11])[NH:12][CH:13]1[CH2:14][CH2:15]1
CC(C)(C)OC(=O)NCc1ccc(F)cc1C(=O)NC1CC1
NCc1ccc(F)cc1C(=O)NC1CC1
null
null
C(Cl)Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C(NC1CC1)c1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[c:3]>>[NH2;D1;+0:1]-[C:2]-[c:3]
100
[{"value": 100.0, "product": "FC(C(=O)O)(F)F.NCC1=C(C(=O)NC2CC2)C=C(C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of tert-butyl 2-(cyclopropylcarbamoyl)-4-fluorobenzylcarbamate (130 mg, 0.42 mmol) prepared according to literature methods, in CH2Cl2 (5 mL) was stirred with trifluoroacetic acid (3 mL) at room temperature for 10 min, then concentrated in vacuo to give 140 mg (Yield 100%) of the title compound as a foam: 1H...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.C1CC1
HO-
C(Cl)Cl
null
null
CC(C)(C)OC(=O)NCc1ccc(F)cc1C(=O)NC1CC1>C(Cl)Cl>NCc1ccc(F)cc1C(=O)NC1CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6d16ec3a7661481db1600a6c44137855
C1COCCN1.Cc1ccc(F)cc1C(=O)Cl>>Cc1ccc(F)cc1C(=O)N1CCOCC1
N1CCOCC1.C(C)N(CC)CC.FC=1C=CC(=C(C(=O)Cl)C1)C>>FC=1C=CC(=C(C1)C(=O)N1CCOCC1)C
[NH:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1.Cl[C:9]([c:8]1[c:2]([CH3:1])[cH:3][cH:4][c:5]([F:6])[cH:7]1)=[O:10]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([F:6])[cH:7][c:8]1[C:9](=[O:10])[N:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1
C1COCCN1.Cc1ccc(F)cc1C(=O)Cl
Cc1ccc(F)cc1C(=O)N1CCOCC1
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
b2821ffedb27fdb32ee8909e6c37f5667f3a9287b29ba6c49c7967ceba44bfc3
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CCOCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1)-[c:3](:[c:4]):[c:5]
98.1
[{"value": 98.0, "product": "FC=1C=CC(=C(C1)C(=O)N1CCOCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.1, "product": "FC=1C=CC(=C(C1)C(=O)N1CCOCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To a solution of morpholine (870 mg, 10 mmol) and triethylamine (1.1 g, 10.8 mmol) in CH2Cl2 (15 mL) was added a solution of 5-fluoro-2-methylbenzoyl chloride (1.72 g, 10 mmol) in CH2Cl2 (5 mL), dropwise, and the mixture stirred for 15 min. The mixture was then washed with water, and the organic phase dried (MgSO4), fi...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1COCCN1
C1COCC[NH]1
c1ccccc1.C1COCC[NH]1
HCl
C(Cl)Cl
null
0.25
C1COCCN1.Cc1ccc(F)cc1C(=O)Cl>C(Cl)Cl>Cc1ccc(F)cc1C(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f400d2481d4e4586a73dfda45b1fec36
Cc1ccc(F)cc1C(=O)N1CCOCC1.O=C1CCC(=O)N1Br>>O=C(c1cc(F)ccc1CBr)N1CCOCC1
C(C1=CC=CC=C1)(=O)OOC(C1=CC=CC=C1)=O.FC=1C=CC(=C(C1)C(=O)N1CCOCC1)C.BrN1C(CCC1=O)=O>>BrCC1=C(C=C(C=C1)F)C(=O)N1CCOCC1
[O:1]=[C:2]([c:3]1[cH:4][c:5]([F:6])[cH:7][cH:8][c:9]1[CH3:10])[N:12]1[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1.O=C1CCC(=O)N1[Br:11]>>[O:1]=[C:2]([c:3]1[cH:4][c:5]([F:6])[cH:7][cH:8][c:9]1[CH2:10][Br:11])[N:12]1[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1
Cc1ccc(F)cc1C(=O)N1CCOCC1.O=C1CCC(=O)N1Br
O=C(c1cc(F)ccc1CBr)N1CCOCC1
null
null
null
Functional Group Interconversion
Wohl-Ziegler bromination benzyl primary
45c0aca0d63a96f0092e6dded9c888827eaf6379dac179e1cefc99293896300a
08f5e7e34d3f321cce3e85421b38226d6240cca0939494ae61032d4f8405cf22
O=C(c1ccccc1)N1CCOCC1
O=C1-C-C-C(=O)-N-1-[Br;H0;D1;+0:1].[#7:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6](-[CH3;D1;+0:7]):[c:8]>>[#7:2]-[C:3](=[O;D1;H0:4])-[c:5]:[c:6](-[CH2;D2;+0:7]-[Br;H0;D1;+0:1]):[c:8]
38.3
[{"value": 38.0, "product": "BrCC1=C(C=C(C=C1)F)C(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.3, "product": "BrCC1=C(C=C(C=C1)F)C(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of intermediate 41, (5-fluoro-2-methylphenyl)(morpholino)methanone, (2.1 g, 9.5 mmol) and N-bromosuccinimide (2.0 g, 11 mmol) in CCl14 (30 mL) was heated at reflux. To this mixture was added benzoylperoxide (242 mg, 1 mmol) and the mixture heated at reflux for 2 hrs. After cooling, the insoluble materials wer...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Primary halide
C1CCNC1
null
c1ccccc1.C1COCC[NH]1
HO-
null
null
null
Cc1ccc(F)cc1C(=O)N1CCOCC1.O=C1CCC(=O)N1Br>>O=C(c1cc(F)ccc1CBr)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f9c750b9df7c47f889d1206627e75429
O=C(c1cc(F)ccc1CBr)N1CCOCC1.[N-]=[N+]=[N-]>>[N-]=[N+]=NCc1ccc(F)cc1C(=O)N1CCOCC1
BrCC1=C(C=C(C=C1)F)C(=O)N1CCOCC1.[N-]=[N+]=[N-].[Na+]>>N(=[N+]=[N-])CC1=C(C=C(C=C1)F)C(=O)N1CCOCC1
Br[CH2:4][c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[C:12](=[O:13])[N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1.[N-:1]=[N+:2]=[N-:3]>>[N-:1]=[N+:2]=[N:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[C:12](=[O:13])[N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1
O=C(c1cc(F)ccc1CBr)N1CCOCC1.[N-]=[N+]=[N-]
[N-]=[N+]=NCc1ccc(F)cc1C(=O)N1CCOCC1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
4b07a4c2a14d792a37e78a751619e60b15c60cbff0bebae1109754fb52d84cbb
2d41632f7225d65cdc2ad8562dfb28f3f5a017f92040ed4ccafbb8154954c8fe
O=C(c1ccccc1)N1CCOCC1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]-[C:5](-[#7:6])=[O;D1;H0:7].[N-;H0;D1:8]=[#7;+:9]=[N;-;D1;H0:10]>>[#7:6]-[C:5](=[O;D1;H0:7])-[c:4]:[c:2](-[CH2;D2;+0:1]-[N;H0;D2;+0:8]=[#7;+:9]=[N;-;D1;H0:10]):[c:3]
88
[{"value": 88.0, "product": "N(=[N+]=[N-])CC1=C(C=C(C=C1)F)C(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.8, "product": "N(=[N+]=[N-])CC1=C(C=C(C=C1)F)C(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of intermediate 42, (2-(bromomethyl)-5-fluorophenyl)(morpholino)methanone, (1.0 g, 3.32 mmol) in dimethylformamide (10 mL) was added sodium azide (230 mg, 3.5 mmol) and the mixture stirred under a nitrogen atmosphere for 1 h. The solvent was evaporated in vacuo, and the residue dissolved in CH2Cl2, then w...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Azide
null
null
c1ccccc1.C1COCC[NH]1
Br-
CN(C=O)C
null
1
O=C(c1cc(F)ccc1CBr)N1CCOCC1.[N-]=[N+]=[N-]>CN(C=O)C>[N-]=[N+]=NCc1ccc(F)cc1C(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ac032dcc7126421b87dbb8808b81f018
CNC.Cc1ccc(F)cc1S(=O)(=O)Cl>>Cc1ccc(F)cc1S(=O)(=O)N(C)C
FC=1C=CC(=C(C1)S(=O)(=O)Cl)C.CNC>>FC=1C=CC(=C(C1)S(=O)(=O)N(C)C)C
[NH:12]([CH3:13])[CH3:14].Cl[S:9]([c:8]1[c:2]([CH3:1])[cH:3][cH:4][c:5]([F:6])[cH:7]1)(=[O:10])=[O:11]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([F:6])[cH:7][c:8]1[S:9](=[O:10])(=[O:11])[N:12]([CH3:13])[CH3:14]
CNC.Cc1ccc(F)cc1S(=O)(=O)Cl
Cc1ccc(F)cc1S(=O)(=O)N(C)C
null
null
O1CCCC1
Miscellaneous
Sulfonamide synthesis (Schotten-Baumann) secondary amine
f885e88ea942f3030166da4c7f20dfb8bf6f1e152c7507d56458611df7dc3120
971e620478d668662a3bf915b510f5704d42a595d6ca9c67de007bd5d7063a75
c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C;D1;H3:7]-[NH;D2;+0:8]-[C;D1;H3:9]>>[C;D1;H3:7]-[N;H0;D3;+0:8](-[C;D1;H3:9])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
90
[{"value": 90.0, "product": "FC=1C=CC(=C(C1)S(=O)(=O)N(C)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
To a solution of 5-fluoro-2-methyl-benzenesulfonyl chloride (4.18 g, 20 mmol) in tetrahydrofuran (25 mL) was added, dropwise, a solution of dimethylamine in tetrahydrofuran (2M, 25 mL, 50 mmol) over 15 min. and the mixture stirred for 5 min. The insoluble materials were filtered and the filtrate concentrated. The resid...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
null
null
c1ccccc1
HCl
O1CCCC1
null
0.083333
CNC.Cc1ccc(F)cc1S(=O)(=O)Cl>O1CCCC1>Cc1ccc(F)cc1S(=O)(=O)N(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-43c328c276064e269b000c1cd2ba1bc1
Cc1ccc(F)cc1S(=O)(=O)N(C)C.O=C1CCC(=O)N1Br>>CN(C)S(=O)(=O)c1cc(F)ccc1CBr
N(=NC(C#N)(C)C)C(C#N)(C)C.FC=1C=CC(=C(C1)S(=O)(=O)N(C)C)C.BrN1C(CCC1=O)=O>>BrCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C
[CH3:1][N:2]([CH3:3])[S:4](=[O:5])(=[O:6])[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[CH3:14].O=C1CCC(=O)N1[Br:15]>>[CH3:1][N:2]([CH3:3])[S:4](=[O:5])(=[O:6])[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[CH2:14][Br:15]
Cc1ccc(F)cc1S(=O)(=O)N(C)C.O=C1CCC(=O)N1Br
CN(C)S(=O)(=O)c1cc(F)ccc1CBr
null
null
C(Cl)(Cl)(Cl)Cl
Functional Group Interconversion
Wohl-Ziegler bromination benzyl primary
45c0aca0d63a96f0092e6dded9c888827eaf6379dac179e1cefc99293896300a
08f5e7e34d3f321cce3e85421b38226d6240cca0939494ae61032d4f8405cf22
c1ccccc1
O=C1-C-C-C(=O)-N-1-[Br;H0;D1;+0:1].[CH3;D1;+0:2]-[c:3](:[c:4]):[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
74.3
[{"value": 74.0, "product": "BrCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.3, "product": "BrCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
5
MINUTE
Under nitrogen, a mixture of intermediate 45, 5-fluoro-2,N,N-trimethyl-benzenesulfonamide, (435 mg, 2.0 mmol) and N-bromosuccinimide (391 mg, 2.2 mmol) in CCl4 (20 mL) was stirred at 80-90° C. for 5 min. To this mixture was added 2,2′-azobisisobutyronitrile (AIBN, 100 mg) and stirring continued at 80-90° C. for 30 min....
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Primary halide
C1CCNC1
null
c1ccccc1
HO-
C(Cl)(Cl)(Cl)Cl
85
0.083333
Cc1ccc(F)cc1S(=O)(=O)N(C)C.O=C1CCC(=O)N1Br>C(Cl)(Cl)(Cl)Cl>CN(C)S(=O)(=O)c1cc(F)ccc1CBr
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae3c707c043f43aca3cf92f8e07f925a
CN(C)S(=O)(=O)c1cc(F)ccc1CBr.[N-]=[N+]=[N-]>>CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]
BrCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C.[N-]=[N+]=[N-].[Na+]>>N(=[N+]=[N-])CC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C
Br[CH2:14][c:13]1[c:7]([S:4]([N:2]([CH3:1])[CH3:3])(=[O:5])=[O:6])[cH:8][c:9]([F:10])[cH:11][cH:12]1.[N-:15]=[N+:16]=[N-:17]>>[CH3:1][N:2]([CH3:3])[S:4](=[O:5])(=[O:6])[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[CH2:14][N:15]=[N+:16]=[N-:17]
CN(C)S(=O)(=O)c1cc(F)ccc1CBr.[N-]=[N+]=[N-]
CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
4b07a4c2a14d792a37e78a751619e60b15c60cbff0bebae1109754fb52d84cbb
2d41632f7225d65cdc2ad8562dfb28f3f5a017f92040ed4ccafbb8154954c8fe
c1ccccc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[N-;H0;D1:5]=[#7;+:6]=[N;-;D1;H0:7]>>[N;-;D1;H0:7]=[#7;+:6]=[N;H0;D2;+0:5]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
87.3
[{"value": 87.0, "product": "N(=[N+]=[N-])CC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.3, "product": "N(=[N+]=[N-])CC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
57.5
CELSIUS
30
MINUTE
A mixture of intermediate 46, 2-bromomethyl-5-fluoro-N,N-dimethyl-benzenesulfonamide, (880 mg, 2.97 mmol) and sodium azide (200 mg, 3 mmol) in dimethylformamide (4 mL) was stirred at 55-60° C. for 30 min after which the solvent was removed in vacuo. The residue was partitioned between CH2Cl2 and water, and the organic ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Azide
null
null
c1ccccc1
Br-
CN(C=O)C
57.5
0.5
CN(C)S(=O)(=O)c1cc(F)ccc1CBr.[N-]=[N+]=[N-]>CN(C=O)C>CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-388c1aca927540cdb94fe526daca40c3
CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]>>CN(C)S(=O)(=O)c1cc(F)ccc1CN
N(=[N+]=[N-])CC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>NCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C
[N-]=[N+]=[N:15][CH2:14][c:13]1[c:7]([S:4]([N:2]([CH3:1])[CH3:3])(=[O:5])=[O:6])[cH:8][c:9]([F:10])[cH:11][cH:12]1>>[CH3:1][N:2]([CH3:3])[S:4](=[O:5])(=[O:6])[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[CH2:14][NH2:15]
CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]
CN(C)S(=O)(=O)c1cc(F)ccc1CN
null
null
O1CCCC1.O
Reduction
Azide to amine reduction (Staudinger)
4c9e4990dae2bb965dec06bd45e318560989ee3681b61e443f7aa363b7cfa222
cd009d687d606bf351eac9390a176d16be38f2c8216a599b398641009c215027
c1ccccc1
[N-]=[N+]=[N;H0;D2;+0:1]-[C:2]-[c:3]>>[NH2;D1;+0:1]-[C:2]-[c:3]
35
[{"value": 35.0, "product": "NCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.0, "product": "NCC1=C(C=C(C=C1)F)S(=O)(=O)N(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
1
HOUR
To a solution of intermediate 47, 2-azidomethyl-5-fluoro-N,N-dimethyl-benzenesulfonamide, (660 mg, 2.6 mmol) in tetrahydrofuran (10 mL) and water (2 mL) was added triphenylphosphine (740 mg, 2.8 mmol), and the mixture stirred under nitrogen for 1 hr. The tetrahydrofuran was evaporated in vacuo and a mixture of the resi...
10.6084/m9.figshare.5104873.v1
null
Azide
Primary amine
null
null
c1ccccc1
Other
O1CCCC1.O
80
1
CN(C)S(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]>O1CCCC1.O>CN(C)S(=O)(=O)c1cc(F)ccc1CN
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a9150065391045dd9e94b001e214dde4
CN.Cc1ccc(F)cc1S(=O)(=O)Cl>>CNS(=O)(=O)c1cc(F)ccc1C
FC=1C=CC(=C(C1)S(=O)(=O)Cl)C.CN>>FC=1C=CC(=C(C1)S(=O)(=O)NC)C
[CH3:1][NH2:2].Cl[S:3](=[O:4])(=[O:5])[c:6]1[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]1[CH3:13]>>[CH3:1][NH:2][S:3](=[O:4])(=[O:5])[c:6]1[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]1[CH3:13]
CN.Cc1ccc(F)cc1S(=O)(=O)Cl
CNS(=O)(=O)c1cc(F)ccc1C
null
null
CC(=O)C
Miscellaneous
Sulfonamide synthesis (Schotten-Baumann) primary amine
a86b0632821e188c0a5dc5a5a2aac298ab3eccaee8a52ba46078c3d5975a290d
50f8fbf3d327483c3eeff8f6cbd4065e4c7600bb501fbe08958a5c79a0926428
c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C;D1;H3:7]-[NH2;D1;+0:8]>>[C;D1;H3:7]-[NH;D2;+0:8]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
96
[{"value": 96.0, "product": "FC=1C=CC(=C(C1)S(=O)(=O)NC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.0, "product": "FC=1C=CC(=C(C1)S(=O)(=O)NC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
To a solution of 5-fluoro-2-methyl-benzenesulfonyl chloride (4.18 g, 20 mmol) in acetone (20 mL) was added a 40% aqueous solution of methylamine (4.5 mL, 60 mmol) under nitrogen and the mixture stirred for 5 min. Acetone was removed in vacuo and the aqueous residue extracted with CH2Cl2. The CH2Cl2 extract was dried (N...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1
HCl
CC(=O)C
null
0.083333
CN.Cc1ccc(F)cc1S(=O)(=O)Cl>CC(=O)C>CNS(=O)(=O)c1cc(F)ccc1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2951742908a2472ab70fe369497278e0
CNS(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]>>CNS(=O)(=O)c1cc(F)ccc1CN
N(=[N+]=[N-])CC1=C(C=C(C=C1)F)S(=O)(=O)NC.Cl>>Cl.NCC1=C(C=C(C=C1)F)S(=O)(=O)NC
[N-]=[N+]=[N:14][CH2:13][c:12]1[c:6]([S:3]([NH:2][CH3:1])(=[O:4])=[O:5])[cH:7][c:8]([F:9])[cH:10][cH:11]1>>[CH3:1][NH:2][S:3](=[O:4])(=[O:5])[c:6]1[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]1[CH2:13][NH2:14]
CNS(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]
CNS(=O)(=O)c1cc(F)ccc1CN
null
[Pd]
C(C)O
Reduction
Azide to amine reduction (Staudinger)
4c9e4990dae2bb965dec06bd45e318560989ee3681b61e443f7aa363b7cfa222
cd009d687d606bf351eac9390a176d16be38f2c8216a599b398641009c215027
c1ccccc1
[N-]=[N+]=[N;H0;D2;+0:1]-[C:2]-[c:3]>>[NH2;D1;+0:1]-[C:2]-[c:3]
100
[{"value": 100.0, "product": "Cl.NCC1=C(C=C(C=C1)F)S(=O)(=O)NC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
14
HOUR
To a solution of intermediate 51, 2-azidomethyl-5-fluoro-N-methyl-benzenesulfonamide, (560 mg, 2.3 mmol) in ethanol (10 mL) was added 6N HCl (1 mL) and 10% Pd—C (100 mg) and the mixture hydrogenated with 1 atm of H2 for 14 hrs. The catalyst was removed by filtration through Celite and the filtrate concentrated in vacuo...
10.6084/m9.figshare.5104873.v1
null
Azide
Primary amine
null
null
c1ccccc1
Other
[Pd].C(C)O
null
14
CNS(=O)(=O)c1cc(F)ccc1CN=[N+]=[N-]>[Pd].C(C)O>CNS(=O)(=O)c1cc(F)ccc1CN
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ddfe96bc6b2a4bb091b82ed029cae0e1
Cc1ccc(F)cc1S(=O)(=O)Cl.[NH4+]>>Cc1ccc(F)cc1S(N)(=O)=O
FC=1C=CC(=C(C1)S(=O)(=O)Cl)C.[NH4+].[OH-]>>FC=1C=CC(=C(C1)S(=O)(=O)N)C
Cl[S:9]([c:8]1[c:2]([CH3:1])[cH:3][cH:4][c:5]([F:6])[cH:7]1)(=[O:11])=[O:12].[NH4+:10]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([F:6])[cH:7][c:8]1[S:9]([NH2:10])(=[O:11])=[O:12]
Cc1ccc(F)cc1S(=O)(=O)Cl.[NH4+]
Cc1ccc(F)cc1S(N)(=O)=O
null
null
CC(=O)C
Functional Group Interconversion
OtherReaction
76fbc3582e2f63736dd65176b79ffad31881adfa34415872457e21307ad3c8dc
8d9fe3486c870d18f12e4e21ee2410d7c9641745d38b34bc61fa11f384cef528
c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH4+;D0:7]>>[NH2;D1;+0:7]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
98
[{"value": 98.0, "product": "FC=1C=CC(=C(C1)S(=O)(=O)N)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 5-fluoro-2-methyl-benzenesulfonyl chloride (4.18 g, 20 mmol) in acetone (20 mL) was added, dropwise, concentrated NH4OH (3 mL) and the resulting mixture stirred for 5 min. Acetone was removed in vacuo and the precipitates were filtered, washed thoroughly with water and dried in vacuo to provide 3.7 g (...
10.6084/m9.figshare.5104873.v1
null
Sulfonyl halide
Sulfonamide
null
null
c1ccccc1
HCl
CC(=O)C
null
null
Cc1ccc(F)cc1S(=O)(=O)Cl.[NH4+]>CC(=O)C>Cc1ccc(F)cc1S(N)(=O)=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-60bd8655d06b42f49624759eec58a5b2
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1>>Cn1nnc(-c2cc(F)ccc2Br)n1
BrC1=C(C=C(C=C1)F)C1=NN=NN1.IC.C([O-])([O-])=O.[K+].[K+]>>BrC1=C(C=C(C=C1)F)C=1N=NN(N1)C
I[CH3:1].[nH:2]1[c:5](-[c:6]2[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]2[Br:13])[n:4][n:3][n:14]1>>[CH3:1][n:2]1[n:3][n:4][c:5](-[c:6]2[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]2[Br:13])[n:14]1
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1
Cn1nnc(-c2cc(F)ccc2Br)n1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
930a6fb6aac3708578433b04494cf2b3154f49b6b8d322e37696a99afead7aa0
7a358c636daddc97c1fb4c29f378044d7eac3f01815d9966e599841f642d631a
c1ccc(-c2nn[nH]n2)cc1
I-[CH3;D1;+0:1].[c:2]:[c:3](-[c;H0;D3;+0:4]1:[#7;a:5]:[n;H0;D2;+0:6]:[n;H0;D2;+0:7]:[nH;D2;+0:8]:1):[c:9]>>[CH3;D1;+0:1]-[n;H0;D3;+0:8]1:[n;H0;D2;+0:7]:[c;H0;D3;+0:4](-[c:3](:[c:2]):[c:9]):[#7;a:5]:[n;H0;D2;+0:6]:1
61.4
[{"value": 61.0, "product": "BrC1=C(C=C(C=C1)F)C=1N=NN(N1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.4, "product": "BrC1=C(C=C(C=C1)F)C=1N=NN(N1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A mixture of 5-(2-bromo-5-fluoro-phenyl)-1H-tetrazole (1.0 g, 4.12 mmol), iodomethane (1.12 g, 10 mmol) and potassium carbonate (1.5 g) in dimethylformamide (5 mL) was stirred at room temperature for 16 hrs, then concentrated in vacuo. The residue was purified by column chromatography (SiO2, CH2Cl2) to provide 650 mg (...
10.6084/m9.figshare.5104873.v1
null
null
null
c1nnn[nH]1
c1nnn[nH]1
c1nnn[nH]1.c1ccccc1
HI
CN(C=O)C
null
16
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1>CN(C=O)C>Cn1nnc(-c2cc(F)ccc2Br)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8f797b4d64954af09da982c4095dd489
Cn1nnc(-c2cc(F)ccc2Br)n1>>Cn1nnc(-c2cc(F)ccc2C#N)n1
BrC1=C(C=C(C=C1)F)C=1N=NN(N1)C.C(#N)[Cu]>>FC1=CC(=C(C#N)C=C1)C=1N=NN(N1)C
Br[c:12]1[c:6](-[c:5]2[n:4][n:3][n:2]([CH3:1])[n:15]2)[cH:7][c:8]([F:9])[cH:10][cH:11]1>>[CH3:1][n:2]1[n:3][n:4][c:5](-[c:6]2[cH:7][c:8]([F:9])[cH:10][cH:11][c:12]2[C:13]#[N:14])[n:15]1
Cn1nnc(-c2cc(F)ccc2Br)n1
Cn1nnc(-c2cc(F)ccc2C#N)n1
null
null
CN(C=O)C
Miscellaneous
OtherReaction
3ae4da8b7f110de99cf8afc091b6f0c8540050148e425770f8030bce1480042c
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccc(-c2nn[nH]n2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[c:5]1:[#7;a:6]:[#7;a:7]:[#7;a:8]:[#7;a:9]:1):[c:10]>>[N;D1;H0:11]#[C:12]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[c:5]1:[#7;a:6]:[#7;a:7]:[#7;a:8]:[#7;a:9]:1):[c:10]
73.8
[{"value": 73.0, "product": "FC1=CC(=C(C#N)C=C1)C=1N=NN(N1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 73.8, "product": "FC1=CC(=C(C#N)C=C1)C=1N=NN(N1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
105
CELSIUS
null
null
A mixture of intermediate 57, 5-(2-bromo-5-fluoro-phenyl)-2-methyl-2H-tetrazole (650 mg, 2.53 mmol) and CuCN (224 mg, 2.5 mmol) in dimethylformamide (4 mL) was placed in a sealed tube and heated at 100-110° C. for 20 hrs. After cooling, the insoluble material was filtered, and the filtrate concentrated in vacuo. The re...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccccc1
c1ccccc1
c1nnn[nH]1.c1ccccc1
Br-
CN(C=O)C
105
null
Cn1nnc(-c2cc(F)ccc2Br)n1>CN(C=O)C>Cn1nnc(-c2cc(F)ccc2C#N)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0524e42510cf4de0bc37d7d302c23ab4
Cn1nnc(-c2cc(F)ccc2C#N)n1>>Cn1nnc(-c2cc(F)ccc2CN)n1
FC1=CC(=C(C#N)C=C1)C=1N=NN(N1)C.Cl>>Cl.FC1=CC(=C(C=C1)CN)C=1N=NN(N1)C
[CH3:2][n:3]1[n:4][n:5][c:6](-[c:7]2[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]2[C:14]#[N:15])[n:16]1>>[CH3:2][n:3]1[n:4][n:5][c:6](-[c:7]2[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]2[CH2:14][NH2:15])[n:16]1
Cn1nnc(-c2cc(F)ccc2C#N)n1
Cn1nnc(-c2cc(F)ccc2CN)n1
null
[Pd]
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
c1ccc(-c2nn[nH]n2)cc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
91
[{"value": 91.0, "product": "Cl.FC1=CC(=C(C=C1)CN)C=1N=NN(N1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A solution of intermediate 58, 4-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-benzonitrile, (330 mg, 1.62 mmol) in ethanol (15 mL) was mixed with 6N HCl (1 mL) and 10% Pd—C (200 mg) under nitrogen. The mixture was then stirred under hydrogen (1 atm) for 3 hrs. After removing the catalyst, the filtrate was concentrated in vacuo...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1nnn[nH]1.c1ccccc1
null
[Pd].C(C)O
null
3
Cn1nnc(-c2cc(F)ccc2C#N)n1>[Pd].C(C)O>Cn1nnc(-c2cc(F)ccc2CN)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a773c69ff8624e18b0f51793686c325a
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1>>CN1NNN=C1c1cc(F)ccc1Br
BrC1=C(C=C(C=C1)F)C1=NN=NN1.IC.C([O-])([O-])=O.[K+].[K+]>>BrC1=C(C=C(C=C1)F)C1=NNNN1C
I[CH3:1].[nH:2]1[n:3][n:4][n:5][c:6]1-[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[Br:14]>>[CH3:1][N:2]1[NH:3][NH:4][N:5]=[C:6]1[c:7]1[cH:8][c:9]([F:10])[cH:11][cH:12][c:13]1[Br:14]
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1
CN1NNN=C1c1cc(F)ccc1Br
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
9f40d716090edf274a06270f0173c4842a11dbd9d7197a72e036e8809b4a71b3
3d5ff1578c40ec948155ee63e26bcd44ed5627e79f81174ca8ffe0dd119c4dba
c1ccc(C2=NNNN2)cc1
I-[CH3;D1;+0:1].[Br;D1;H0:2]-[c:3](:[c:4]):[c;H0;D3;+0:5](-[c;H0;D3;+0:6]1:[n;H0;D2;+0:7]:[n;H0;D2;+0:8]:[n;H0;D2;+0:9]:[nH;D2;+0:10]:1):[c:11]:[c:12]>>[Br;D1;H0:2]-[c:3](:[c:4]):[c;H0;D3;+0:5](-[C;H0;D3;+0:6]1=[N;H0;D2;+0:7]-[NH;D2;+0:8]-[NH;D2;+0:9]-[N;H0;D3;+0:10]-1-[CH3;D1;+0:1]):[c:11]:[c:12]
33
[{"value": 33.0, "product": "BrC1=C(C=C(C=C1)F)C1=NNNN1C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 32.8, "product": "BrC1=C(C=C(C=C1)F)C1=NNNN1C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A mixture of 5-(2-bromo-5-fluoro-phenyl)-1H-tetrazole (1.0 g, 4.12 mmol), iodomethane (1.12 g, 10 mmol) and potassium carbonate (1.5 g) in dimethylformamide (5 mL) was stirred at room temperature for 16 hrs, then concentrated in vacuo. The residue was purified by column chromatography (SiO2, CH2Cl2) to provide 350 mg (...
10.6084/m9.figshare.5104873.v1
null
null
Hydrazine.Hydrazine.Hydrazone
c1nnn[nH]1
C1=NNN[NH]1
C1=NNN[NH]1.c1ccccc1
I-
CN(C=O)C
null
16
CI.Fc1ccc(Br)c(-c2nnn[nH]2)c1>CN(C=O)C>CN1NNN=C1c1cc(F)ccc1Br
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-81c87b1311544d9497322a7ff86f5b41
Cc1cccc(C2(C(F)(F)F)NN2)c1>>Cc1cccc(C2(C(F)(F)F)N=N2)c1
S(=O)([O-])[O-].[Na+].[Na+].C(C)N(CC)CC.C1(=CC(=CC=C1)C1(NN1)C(F)(F)F)C.ClOC(C)(C)C>>C1(=CC(=CC=C1)C1(N=N1)C(F)(F)F)C
[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]([C:7]2([C:8]([F:9])([F:10])[F:11])[NH:12][NH:13]2)[cH:14]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]([C:7]2([C:8]([F:9])([F:10])[F:11])[N:12]=[N:13]2)[cH:14]1
Cc1cccc(C2(C(F)(F)F)NN2)c1
Cc1cccc(C2(C(F)(F)F)N=N2)c1
null
null
C(C)O
Oxidation
OtherReaction
d4c1c5f2d88466e394c71fa23b4075bc66d1d54dd18a34ff41659f0abcd991a3
af0c3c0cbdc6de6fea6137c38d32e5f7501ca840baaaf07cf656287a9aaca482
c1ccc(C2N=N2)cc1
[F;D1;H0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[C:5]1(-[c:6])-[NH;D2;+0:7]-[NH;D2;+0:8]-1>>[F;D1;H0:1]-[C:2](-[F;D1;H0:3])(-[F;D1;H0:4])-[C:5]1(-[c:6])-[N;H0;D2;+0:7]=[N;H0;D2;+0:8]-1
80
[{"value": 80.0, "product": "C1(=CC(=CC=C1)C1(N=N1)C(F)(F)F)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
To a cold stirring solution of 3-m-tolyl-3-trifluoromethyl-diaziridine (2.0 g, 10 mmol. prepared using the methods described in Doucet-Personeni C. et al., J. Med. Chem., 2001, 44, 3203 and Nassal, M. Liebigs Ann. Chem. 1983, 1510-1523 or in Stromgaard, K et al., J. Med. Chem., 2002, 45, 4038-46) in ethanol (20 mL) was...
10.6084/m9.figshare.5104873.v1
null
Hydrazine
Diazene
C1NN1
C1N=N1
c1ccccc1.C1N=N1
null
C(C)O
null
0.083333
Cc1cccc(C2(C(F)(F)F)NN2)c1>C(C)O>Cc1cccc(C2(C(F)(F)F)N=N2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7965cd4c675942eaa86bbab692b71822
Cc1cccc(C2(C(F)(F)F)N=N2)c1.O=C1CCC(=O)N1Br>>FC(F)(F)C1(c2cccc(CBr)c2)N=N1
CC(C)(C#N)N=NC(C)(C)C#N.C1(=CC(=CC=C1)C1(N=N1)C(F)(F)F)C.BrN1C(CCC1=O)=O>>BrCC=1C=C(C=CC1)C1(N=N1)C(F)(F)F
[F:1][C:2]([F:3])([F:4])[C:5]1([c:6]2[cH:7][cH:8][cH:9][c:10]([CH3:11])[cH:13]2)[N:14]=[N:15]1.O=C1CCC(=O)N1[Br:12]>>[F:1][C:2]([F:3])([F:4])[C:5]1([c:6]2[cH:7][cH:8][cH:9][c:10]([CH2:11][Br:12])[cH:13]2)[N:14]=[N:15]1
Cc1cccc(C2(C(F)(F)F)N=N2)c1.O=C1CCC(=O)N1Br
FC(F)(F)C1(c2cccc(CBr)c2)N=N1
null
null
C(Cl)(Cl)(Cl)Cl
Functional Group Interconversion
Wohl-Ziegler bromination benzyl primary
45c0aca0d63a96f0092e6dded9c888827eaf6379dac179e1cefc99293896300a
08f5e7e34d3f321cce3e85421b38226d6240cca0939494ae61032d4f8405cf22
c1ccc(C2N=N2)cc1
O=C1-C-C-C(=O)-N-1-[Br;H0;D1;+0:1].[CH3;D1;+0:2]-[c:3](:[c:4]):[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
54
[{"value": 54.0, "product": "BrCC=1C=C(C=CC1)C1(N=N1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.8, "product": "BrCC=1C=C(C=CC1)C1(N=N1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
null
null
To a solution of intermediate 63, 3-m-tolyl-3-trifluoromethyl-3H-diazirine, (200 mg, 1 mmol) in CCl4 (4 mL) was added N-bromosuccinimide (200 mg, 1.1 mmol, re-crystallized from water), and the stirred mixture heated at 85° C. To this was added AIBN (50 mg) and the mixture heated at reflux for an additional 2.5 hrs. Aft...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Primary halide
C1CCNC1
null
c1ccccc1.C1N=N1
HO-
C(Cl)(Cl)(Cl)Cl
85
null
Cc1cccc(C2(C(F)(F)F)N=N2)c1.O=C1CCC(=O)N1Br>C(Cl)(Cl)(Cl)Cl>FC(F)(F)C1(c2cccc(CBr)c2)N=N1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-37b72579dd824e4e8d39d5470bd1b8ce
FC(F)(F)C1(c2cccc(CBr)c2)N=N1.O=C1NC(=O)c2ccccc21>>O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1
BrCC=1C=C(C=CC1)C1(N=N1)C(F)(F)F.C1(C=2C(C(N1)=O)=CC=CC2)=O.[K]>>FC(C1(NN1)C=1C=C(CN2C(C3=CC=CC=C3C2=O)=O)C=CC1)(F)F
Br[CH2:12][c:13]1[cH:14][cH:15][cH:16][c:17]([C:18]2([C:19]([F:20])([F:21])[F:22])[N:23]=[N:24]2)[cH:25]1.[O:1]=[C:2]1[c:3]2[cH:4][cH:5][cH:6][cH:7][c:8]2[C:9](=[O:10])[NH:11]1>>[O:1]=[C:2]1[c:3]2[cH:4][cH:5][cH:6][cH:7][c:8]2[C:9](=[O:10])[N:11]1[CH2:12][c:13]1[cH:14][cH:15][cH:16][c:17]([C:18]2([C:19]([F:20])([F:21])...
FC(F)(F)C1(c2cccc(CBr)c2)N=N1.O=C1NC(=O)c2ccccc21
O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
4c865fab9d111ad9e304f11b498345c27f408e173c6a7bf6511a237bc5654553
8b90dd121a9459404c29e364a2a5e48a7f20b27e963729932413919d6eb85963
O=C1c2ccccc2C(=O)N1Cc1cccc(C2NN2)c1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]-[C:6]1(-[C:7](-[F;D1;H0:8])(-[F;D1;H0:9])-[F;D1;H0:10])-[N;H0;D2;+0:11]=[N;H0;D2;+0:12]-1.[O;D1;H0:13]=[C:14]1-[NH;D2;+0:15]-[C:16](=[O;D1;H0:17])-[c:18]:[c:19]-1>>[F;D1;H0:8]-[C:7](-[F;D1;H0:9])(-[F;D1;H0:10])-[C:6]1(-[c:5]:[c:4]:[c:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:15]2-[C:16](=...
82
[{"value": 82.0, "product": "FC(C1(NN1)C=1C=C(CN2C(C3=CC=CC=C3C2=O)=O)C=CC1)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.6, "product": "FC(C1(NN1)C=1C=C(CN2C(C3=CC=CC=C3C2=O)=O)C=CC1)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A mixture of intermediate 64, 3-(3-bromomethyl-phenyl)-3-trifluoromethyl-3H-diazirine, (140 mg, 0.5 mmol) and potassium phthalimide (95 mg, 0.5 mmol) in dimethylformamide (1.5 mL) was stirred at room temperature for 3 hrs. Dimethylformamide was removed in vacuo. The residue was extracted with CH2Cl2, washed with water,...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Diazene.Unsubstituted dicarboximide
Hydrazine.Substituted dicarboximide
C1N=N1.c1ccc2c(c1)CNC2
c1ccc2c(c1)C[NH]C2.C1NN1
c1ccc2c(c1)C[NH]C2.c1ccccc1.C1NN1
Br-
CN(C=O)C
null
3
FC(F)(F)C1(c2cccc(CBr)c2)N=N1.O=C1NC(=O)c2ccccc21>CN(C=O)C>O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-aaa5aabaae534c5d815aeb623e07bc90
O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1>>NCc1cccc(C2(C(F)(F)F)NN2)c1
FC(C1(NN1)C=1C=C(CN2C(C3=CC=CC=C3C2=O)=O)C=CC1)(F)F.O.NN.FC(C1(N=N1)C=1C=C(C=CC1)CN)(F)F>>FC(C1(NN1)C=1C=C(C=CC1)CN)(F)F
O=C1c2ccccc2C(=O)[N:1]1[CH2:2][c:3]1[cH:4][cH:5][cH:6][c:7]([C:8]2([C:9]([F:10])([F:11])[F:12])[NH:13][NH:14]2)[cH:15]1>>[NH2:1][CH2:2][c:3]1[cH:4][cH:5][cH:6][c:7]([C:8]2([C:9]([F:10])([F:11])[F:12])[NH:13][NH:14]2)[cH:15]1
O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1
NCc1cccc(C2(C(F)(F)F)NN2)c1
null
null
C(C)O
Reduction
Phthalimide deprotection
d9f63cee80ef758bd939ff2a10772447b3092f1576180488281833a98eb1691a
dbfe4201a9328005dfaec4c3f363ddbb4ef3c9b825f648735dc97b2b57396333
c1ccc(C2NN2)cc1
O=C1-[N;H0;D3;+0:1](-[C:2]-[c:3])-C(=O)-c2:c:c:c:c:c:2-1>>[NH2;D1;+0:1]-[C:2]-[c:3]
54
[{"value": 54.0, "product": "FC(C1(NN1)C=1C=C(C=CC1)CN)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.5, "product": "FC(C1(NN1)C=1C=C(C=CC1)CN)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3.5
HOUR
A stirred solution of intermediate 65, 2-[3-(3-trifluoromethyl-diaziridin-3-yl)-benzyl]-isoindole-1,3-dione, (150 mg, 0.43 mmol) in ethanol (2 mL) was treated with hydrazine hydrate (0.4 mL) at room temperature and the solution stirred for 3.5 hrs. After removing ethanol in vacuo, the residue was partitioned between CH...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
Primary amine
c1ccc2c(c1)C[NH]C2
null
c1ccccc1.C1NN1
HO-
C(C)O
null
3.5
O=C1c2ccccc2C(=O)N1Cc1cccc(C2(C(F)(F)F)NN2)c1>C(C)O>NCc1cccc(C2(C(F)(F)F)NN2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ea34a7e330bd406f98bf6c5b058cab7f
N#Cc1ccc(F)cc1-n1cncn1.NCc1ccc(F)cc1-n1cncn1>>N#Cc1ccc(-n2cncn2)cc1F
FC1=CC(=C(C#N)C=C1)N1N=CN=C1.Cl.Cl.FC1=CC(=C(C=C1)CN)N1N=CN=C1>>N1(N=CN=C1)C1=CC(=C(C#N)C=C1)F
c1ncn(-[c:13]2[c:3]([C:2]#[N:1])[cH:4][cH:5][c:6]([F:14])[cH:12]2)n1.NCc1ccc(F)cc1-[n:7]1[cH:8][n:9][cH:10][n:11]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6](-[n:7]2[cH:8][n:9][cH:10][n:11]2)[cH:12][c:13]1[F:14]
N#Cc1ccc(F)cc1-n1cncn1.NCc1ccc(F)cc1-n1cncn1
N#Cc1ccc(-n2cncn2)cc1F
null
[Pd]
C(C)O
Functional Group Interconversion
OtherReaction
1f1872775e17cb8e244c6640d13c32fd86cc500cb3ea463805aab065e2391190
5f74ebbd0d40da38f38937c5d779c9d8b532f0902c1ada6a7de5154c23d802dd
c1ccc(-n2cncn2)cc1
F-c1:c:c:c(-C-N):c(-[n;H0;D3;+0:1]2:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]:2):c:1.[F;H0;D1;+0:6]-[c;H0;D3;+0:7]1:[c:8]:[c;H0;D3;+0:9](-n2:c:n:c:n:2):[c:10](-[C:11]#[N;D1;H0:12]):[c:13]:[c:14]:1>>[F;H0;D1;+0:6]-[c;H0;D3;+0:9]1:[c:8]:[c;H0;D3;+0:7](-[n;H0;D3;+0:1]2:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]:2):[c:14]:[c:13]:[c:10]:1-[C:11]#[N...
99
[{"value": 99.0, "product": "N1(N=CN=C1)C1=CC(=C(C#N)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
(4-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)methanamine hydrochloride). Intermediate 67, 4-fluoro-2-(1H-1,2,4-triazol-1-yl)benzonitrile, (2.46 g, 13.13 mmol) was dissolved in hot ethanol (150 mL). To this was added 1N HCl (15 mL) followed by 10% Pd—C (200 mg). The mixture was treated with H2 at 55 psi for 4 h in a Parr s...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Primary amine
Aromatic halide
c1nnc[nH]1.c1ccccc1.c1ccccc1.c1nc[nH]n1
c1ccccc1.c1nc[nH]n1
c1ccccc1.c1nc[nH]n1
HF
[Pd].C(C)O
null
null
N#Cc1ccc(F)cc1-n1cncn1.NCc1ccc(F)cc1-n1cncn1>[Pd].C(C)O>N#Cc1ccc(-n2cncn2)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2f40c7874c25448d95e5a817868bbd87
N#Cc1ccc(F)cc1N1CCCCS1(=O)=O>>NCc1ccc(F)cc1N1CCCCS1(=O)=O
FC1=CC(=C(C#N)C=C1)N1S(CCCC1)(=O)=O.Cl>>Cl.FC1=CC(=C(C=C1)CN)N1S(CCCC1)(=O)=O
[N:2]#[C:3][c:4]1[cH:5][cH:6][c:7]([F:8])[cH:9][c:10]1[N:11]1[CH2:12][CH2:13][CH2:14][CH2:15][S:16]1(=[O:17])=[O:18]>>[NH2:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([F:8])[cH:9][c:10]1[N:11]1[CH2:12][CH2:13][CH2:14][CH2:15][S:16]1(=[O:17])=[O:18]
N#Cc1ccc(F)cc1N1CCCCS1(=O)=O
NCc1ccc(F)cc1N1CCCCS1(=O)=O
null
[Pd]
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
O=S1(=O)CCCCN1c1ccccc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
100
[{"value": 100.0, "product": "Cl.FC1=CC(=C(C=C1)CN)N1S(CCCC1)(=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
Intermediate 75, 4-fluoro-2-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)benzonitrile (1.37 g, 5.4 mmol) was dissolved in ethanol (120 mL). To this was added 1N HCl (20 mL) and a catalytic amount of 10% Pd—C. The mixture was shaken under hydrogen at 55 psi for 4 h then filtered through Celite and concentrated to give the title c...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1.C1CCS[NH]C1
null
[Pd].C(C)O
null
4
N#Cc1ccc(F)cc1N1CCCCS1(=O)=O>[Pd].C(C)O>NCc1ccc(F)cc1N1CCCCS1(=O)=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-506faeaea3484a76b0b18dc850a6b2c1
N#Cc1ccc(F)cc1-n1nccn1>>NCc1ccc(F)cc1-n1nccn1
Cl.FC1=CC(=C(C#N)C=C1)N1N=CC=N1>>Cl.FC1=CC(=C(CN)C=C1)N1N=CC=N1
[N:2]#[C:3][c:4]1[cH:5][cH:6][c:7]([F:8])[cH:9][c:10]1-[n:11]1[n:12][cH:13][cH:14][n:15]1>>[NH2:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([F:8])[cH:9][c:10]1-[n:11]1[n:12][cH:13][cH:14][n:15]1
N#Cc1ccc(F)cc1-n1nccn1
NCc1ccc(F)cc1-n1nccn1
null
[Pd]
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
c1ccc(-n2nccn2)cc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
null
[]
null
null
4
HOUR
Intermediate 77, 4-fluoro-2-1,2,3-triazol-2-yl-benzonitrile, (0.34 g, 1.8 mmol) was dissolved in ethanol (50 mL). 1N HCl (10 mL) was added along with a catalytic amount of 10%-Pd—C. The mixture was shaken under H2 at 55 psi for 4 h after which it was filtered through Celite and concentrated to give the title compound a...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1.c1c[nH]nn1
null
[Pd].C(C)O
null
4
N#Cc1ccc(F)cc1-n1nccn1>[Pd].C(C)O>NCc1ccc(F)cc1-n1nccn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-66586bd856364f78a42cba315020169c
N#Cc1ccc(F)cc1F.c1c[nH]cn1>>N#Cc1ccc(F)cc1-n1ccnc1
N1C=NC=C1.C([O-])([O-])=O.[K+].[K+].FC1=C(C#N)C=CC(=C1)F>>FC1=CC(=C(C#N)C=C1)N1C=NC=C1
F[c:9]1[c:3]([C:2]#[N:1])[cH:4][cH:5][c:6]([F:7])[cH:8]1.[nH:10]1[cH:11][cH:12][n:13][cH:14]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([F:7])[cH:8][c:9]1-[n:10]1[cH:11][cH:12][n:13][cH:14]1
N#Cc1ccc(F)cc1F.c1c[nH]cn1
N#Cc1ccc(F)cc1-n1ccnc1
null
null
O1CCCC1.CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
b282a5e1885a37e36f5b39b22cb06585a64583e50efbafa1ce368e9c3dbc55f3
e3660767655c50df0f92afc78c794dd2af7cf646bf1430960eafd30c23bf3fa7
c1ccc(-n2ccnc2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5]#[N;D1;H0:6]):[c:7].[#7;a:8]1:[c:9]:[c:10]:[nH;D2;+0:11]:[c:12]:1>>[N;D1;H0:6]#[C:5]-[c:4](:[c:7]):[c;H0;D3;+0:1](-[n;H0;D3;+0:11]1:[c:10]:[c:9]:[#7;a:8]:[c:12]:1):[c:2]:[c:3]
9
[{"value": 9.0, "product": "FC1=CC(=C(C#N)C=C1)N1C=NC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 9.0, "product": "FC1=CC(=C(C#N)C=C1)N1C=NC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of imidazole (4.45 g, 65.4 mmol) in tetrahydrofuran (30 mL) and dimethylformamide (10 mL) was added potassium carbonate (9.95 g, 72 mmol) and the mixture was stirred for 30 min at room temp. To this was added 2,4-difluorobenzonitrile (10.0 g, 72 mmol) and the mixture stirred at 90° C. for 3 h then at room...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1.c1c[nH]cn1
c1ccccc1.c1c[nH]cn1
c1ccccc1.c1c[nH]cn1
HF
O1CCCC1.CN(C=O)C
null
0.5
N#Cc1ccc(F)cc1F.c1c[nH]cn1>O1CCCC1.CN(C=O)C>N#Cc1ccc(F)cc1-n1ccnc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-992c8966662e45b99992fe347fd506a7
N#Cc1cc(F)ccc1F.c1nc[nH]n1>>N#Cc1cc(F)ccc1-n1cncn1
FC1=C(C#N)C=C(C=C1)F.[Na].N1N=CN=C1>>FC=1C=CC(=C(C#N)C1)N1N=CN=C1
F[c:9]1[c:3]([C:2]#[N:1])[cH:4][c:5]([F:6])[cH:7][cH:8]1.[nH:10]1[cH:11][n:12][cH:13][n:14]1>>[N:1]#[C:2][c:3]1[cH:4][c:5]([F:6])[cH:7][cH:8][c:9]1-[n:10]1[cH:11][n:12][cH:13][n:14]1
N#Cc1cc(F)ccc1F.c1nc[nH]n1
N#Cc1cc(F)ccc1-n1cncn1
null
null
CN(C=O)C.C(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
dff1d318970a706943117b26793c51edded6a9a33120b190609ee0c5e3cf31e9
e3660767655c50df0f92afc78c794dd2af7cf646bf1430960eafd30c23bf3fa7
c1ccc(-n2cncn2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5]#[N;D1;H0:6]):[c:7].[#7;a:8]1:[c:9]:[nH;D2;+0:10]:[#7;a:11]:[c:12]:1>>[N;D1;H0:6]#[C:5]-[c:4](:[c:7]):[c;H0;D3;+0:1](-[n;H0;D3;+0:10]1:[#7;a:11]:[c:12]:[#7;a:8]:[c:9]:1):[c:2]:[c:3]
49
[{"value": 49.0, "product": "FC=1C=CC(=C(C#N)C1)N1N=CN=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.0, "product": "FC=1C=CC(=C(C#N)C1)N1N=CN=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A suspension of 2,5-diflurobenzonitrile (4.5 g, 32.35 mmol) and 1,2,4-triazole sodium salt (3.6 g, 40 mmol) in dimethylformamide (40 mL) was heated at 80° C. for 15 h. The reaction mixture was then cooled, diluted with CH2Cl2 (200 mL), washed with water (3×30 mL) and brine (30 mL), then dried (Na2SO4), filtered and con...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1.c1nc[nH]n1
c1ccccc1.c1nc[nH]n1
c1ccccc1.c1nc[nH]n1
HF
CN(C=O)C.C(Cl)Cl
80
null
N#Cc1cc(F)ccc1F.c1nc[nH]n1>CN(C=O)C.C(Cl)Cl>N#Cc1cc(F)ccc1-n1cncn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d1a4f8e5372a424cab5cc30d6f794e58
N#Cc1cc(F)ccc1-n1cncn1>>NCc1cc(F)ccc1-n1cncn1
FC=1C=CC(=C(C#N)C1)N1N=CN=C1.Cl>>Cl.FC=1C=CC(=C(C1)CN)N1N=CN=C1
[N:2]#[C:3][c:4]1[cH:5][c:6]([F:7])[cH:8][cH:9][c:10]1-[n:11]1[cH:12][n:13][cH:14][n:15]1>>[NH2:2][CH2:3][c:4]1[cH:5][c:6]([F:7])[cH:8][cH:9][c:10]1-[n:11]1[cH:12][n:13][cH:14][n:15]1
N#Cc1cc(F)ccc1-n1cncn1
NCc1cc(F)ccc1-n1cncn1
null
null
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
c1ccc(-n2cncn2)cc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
98
[{"value": 98.0, "product": "Cl.FC=1C=CC(=C(C1)CN)N1N=CN=C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
A solution of intermediate 96, 5-fluoro-2-(1H-1,2,4-triazol-1-yl)benzonitrile (2.94 g, 15.59 mmol) in ethanol (100 mL) and 1N HCl (50 mL) was degassed by bubbling N2. Then, 10%Pd/C was added, the flask evacuated and vented to H2 three times and left on a Parr shaker under a H2 atmosphere (40 psi). After 6 h, the reacti...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1.c1nc[nH]n1
null
C(C)O
null
6
N#Cc1cc(F)ccc1-n1cncn1>C(C)O>NCc1cc(F)ccc1-n1cncn1