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-9b4501613ebb4ca9b57b37a0651b562c
COc1cc(-c2nc3sccn3c2C(=O)C=CN(C)C)ccc1F.[H]/N=C(/N)NC1CCN(C(=O)OC(C)(C)C)CC1>>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F
[O-]CC.[Na+].CN(C=CC(=O)C1=C(N=C2SC=CN21)C2=CC(=C(C=C2)F)OC)C.Cl.N/C(=N/[H])/NC1CCN(CC1)C(=O)OC(C)(C)C>>FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCN(CC1)C(=O)OC(C)(C)C)OC
CN(C)[CH:16]=[CH:15][C:14](=O)[c:13]1[c:6](-[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:36]([F:37])[cH:35][cH:34]2)[n:7][c:8]2[s:9][cH:10][cH:11][n:12]21.[H]/[N:17]=[C:18](\[NH:19][CH:20]1[CH2:21][CH2:22][N:23]([C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH2:31][CH2:32]1)[NH2:33]>>[CH3:1][O:2][c:3]1[cH:4][c:5](-[c:6...
COc1cc(-c2nc3sccn3c2C(=O)C=CN(C)C)ccc1F.[H]/N=C(/N)NC1CCN(C(=O)OC(C)(C)C)CC1
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
78274536798da2b99a51ce47d0994df99b4d5455af910301779a9ae5938608b5
11da551d0a7bf93f6d300d0e461ec1d4a2060497908163f95323146dc93cd499
c1ccc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)cc1
C-N(-C)-[CH;D2;+0:1]=[CH;D2;+0:2]-[C;H0;D3;+0:3](=O)-[c;H0;D3;+0:4]1:[#7;a:5]2:[c:6]:[c:7]:[#16;a:8]:[c:9]:2:[#7;a:10]:[c:11]:1-[c:12].[C:13]-[#7:14]/[C;H0;D3;+0:15](-[NH2;D1;+0:16])=[N;H0;D2;+0:17]\[H]>>[C:13]-[#7:14]-[c;H0;D3;+0:15]1:[n;H0;D2;+0:17]:[cH;D2;+0:1]:[cH;D2;+0:2]:[c;H0;D3;+0:3](-[c;H0;D3;+0:4]2:[#7;a:5]3:...
88
[{"value": 88.0, "product": "FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCN(CC1)C(=O)OC(C)(C)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.7, "product": "FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCN(CC1)C(=O)OC(C)(C)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 3-(dimethylamino)-1-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]prop-2-en-1-one (0.537 g, 1.55 mmol) and tert-butyl 4-{[(Z)-amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride (0.650 g, 2.33 mmol) was diluted with 13 ml of absolute ethanol and treated with 1.35 eq. of a 21% w/w...
10.6084/m9.figshare.5104873.v1
null
Enamine.Ketone.Primary amine
null
null
c1cncnc1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1
HO-
C(C)O
null
null
COc1cc(-c2nc3sccn3c2C(=O)C=CN(C)C)ccc1F.[H]/N=C(/N)NC1CCN(C(=O)OC(C)(C)C)CC1>C(C)O>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d24943ef497042baa68dee089eabafa4
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F>>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F
FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCN(CC1)C(=O)OC(C)(C)C)OC.Cl>>Cl.FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCNCC1)OC
CC(C)(C)OC(=O)[N:23]1[CH2:22][CH2:21][CH:20]([NH:19][c:18]2[n:17][cH:16][cH:15][c:14](-[c:13]3[c:6](-[c:5]4[cH:4][c:3]([O:2][CH3:1])[c:29]([F:30])[cH:28][cH:27]4)[n:7][c:8]4[s:9][cH:10][cH:11][n:12]43)[n:26]2)[CH2:25][CH2:24]1>>[CH3:1][O:2][c:3]1[cH:4][c:5](-[c:6]2[n:7][c:8]3[s:9][cH:10][cH:11][n:12]3[c:13]2-[c:14]2[cH...
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F
null
null
O1CCOCC1.CCOCC
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
96
[{"value": 96.0, "product": "Cl.FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCNCC1)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
The tert-butyl 4-({4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylate (0.713 g, 1.36 mmol) was dissolved in 15 ml of dioxane and treated with 7.5 ml of anhydrous 4N HCl in dioxane at room temperature (RT). The reaction mixture was stirred at room temperature for...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CCNCC1
HO-
O1CCOCC1.CCOCC
null
2
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(C(=O)OC(C)(C)C)CC3)n2)ccc1F>O1CCOCC1.CCOCC>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-099ff9a3f7c245db8c7687562bf78285
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F.O=S(=O)(Cl)C1CC1>>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F
Cl.FC1=C(C=C(C=C1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)NC1CCNCC1)OC.CCN(C(C)C)C(C)C.C1(CC1)S(=O)(=O)Cl>>C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=C(C=C2)F)OC
[CH3:1][O:2][c:3]1[cH:4][c:5](-[c:6]2[n:7][c:8]3[s:9][cH:10][cH:11][n:12]3[c:13]2-[c:14]2[cH:15][cH:16][n:17][c:18]([NH:19][CH:20]3[CH2:21][CH2:22][NH:23][CH2:30][CH2:31]3)[n:32]2)[cH:33][cH:34][c:35]1[F:36].Cl[S:24](=[O:25])(=[O:26])[CH:27]1[CH2:28][CH2:29]1>>[CH3:1][O:2][c:3]1[cH:4][c:5](-[c:6]2[n:7][c:8]3[s:9][cH:10...
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F.O=S(=O)(Cl)C1CC1
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F
null
null
C(Cl)Cl
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
d63e07b47df62aebedb35134f6d0504cfcbed5ccfdec31c2c42bba6875c15fe7
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=S(=O)(C1CC1)N1CCC(Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)CC1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4]1-[C:5]-[C:6]-1.[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]>>[C:7]-[C:8]-[N;H0;D3;+0:9](-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4]1-[C:5]-[C:6]-1)-[C:10]-[C:11]
96
[{"value": 96.0, "product": "C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=C(C=C2)F)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.7, "product": "C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=C(C=C2)F)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
The 4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[piperidin-4-yl]pyrimidin-2-amine hydrochloride (0.25 g, 0.50 mmol) in methylene chloride (DCM) (12 ml) was cooled to 0° C. and was treated with Hunig's base (440 μl, 2.5 mmol). The mixture was kept at 0° C. for 30 minutes then the cyclopropyl-sulfon...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.C1CC1
HCl
C(Cl)Cl
null
0.5
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCNCC3)n2)ccc1F.O=S(=O)(Cl)C1CC1>C(Cl)Cl>COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e48581f19f644b8a9f2e315f6deca415
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F>>O=S(=O)(C1CC1)N1CCC(Nc2nccc(-c3c(-c4ccc(F)c(O)c4)nc4sccn34)n2)CC1
B(Br)(Br)Br.C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=C(C=C2)F)OC>>C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=CC(=C(C2)O)F
C[O:25][c:24]1[c:22]([F:23])[cH:21][cH:20][c:19](-[c:18]2[c:17](-[c:16]3[cH:15][cH:14][n:13][c:12]([NH:11][CH:10]4[CH2:9][CH2:8][N:7]([S:2](=[O:1])(=[O:3])[CH:4]5[CH2:5][CH2:6]5)[CH2:35][CH2:34]4)[n:33]3)[n:32]3[c:28]([n:27]2)[s:29][cH:30][cH:31]3)[cH:26]1>>[O:1]=[S:2](=[O:3])([CH:4]1[CH2:5][CH2:6]1)[N:7]1[CH2:8][CH2:9...
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F
O=S(=O)(C1CC1)N1CCC(Nc2nccc(-c3c(-c4ccc(F)c(O)c4)nc4sccn34)n2)CC1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=S(=O)(C1CC1)N1CCC(Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)CC1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
86
[{"value": 86.0, "product": "C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=CC(=C(C2)O)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 85.9, "product": "C1(CC1)S(=O)(=O)N1CCC(CC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=CC(=C(C2)O)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
The N-[1-(cyclopropylsulfonyl)piperidin-4-yl]-4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.226 g, 0.43 mmol) in methylene chloride (8 ml) was cooled to −78° C. and slowly treated with 1 molar solution of boron tribromide in methylene chloride (3.4 ml). The reaction mixture was kep...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
C1CC1.C1CC[NH]CC1.c1cncnc1.c1ccccc1.c1cn2ccsc2n1
Other
C(Cl)Cl
null
1
COc1cc(-c2nc3sccn3c2-c2ccnc(NC3CCN(S(=O)(=O)C4CC4)CC3)n2)ccc1F>C(Cl)Cl>O=S(=O)(C1CC1)N1CCC(Nc2nccc(-c3c(-c4ccc(F)c(O)c4)nc4sccn34)n2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d81fd74075da410cb9bfee6494225657
N#Cc1cccc(C(=O)CBr)c1.Nc1nccs1>>N#Cc1cccc(-c2cn3ccsc3n2)c1
NC=1SC=CN1.BrCC(=O)C1=CC(=CC=C1)C#N.[OH-].[NH4+]>>C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1
O=[C:8]([c:7]1[cH:6][cH:5][cH:4][c:3]([C:2]#[N:1])[cH:16]1)[CH2:9]Br.[n:10]1[cH:11][cH:12][s:13][c:14]1[NH2:15]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][cH:6][c:7](-[c:8]2[cH:9][n:10]3[cH:11][cH:12][s:13][c:14]3[n:15]2)[cH:16]1
N#Cc1cccc(C(=O)CBr)c1.Nc1nccs1
N#Cc1cccc(-c2cn3ccsc3n2)c1
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
fc4245e28231e2acdadf0a109add94d7bcbb15727aa9b3c4274dbbacfc4598a4
9e77d52183fdbe84f0d2ab96039aaf521caea9340e743bdc6436175f1a3bbdb6
c1ccc(-c2cn3ccsc3n2)cc1
Br-[CH2;D2;+0:1]-[C;H0;D3;+0:2](=O)-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7].[NH2;D1;+0:8]-[c:9]1:[#16;a:10]:[c:11]:[c:12]:[n;H0;D2;+0:13]:1>>[c:5]:[c:4]:[c;H0;D3;+0:3](-[c;H0;D3;+0:2]1:[cH;D2;+0:1]:[n;H0;D3;+0:13]2:[c:12]:[c:11]:[#16;a:10]:[c:9]:2:[n;H0;D2;+0:8]:1):[c:6]:[c:7]
81
[{"value": 81.0, "product": "C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.0, "product": "C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
To a mixture of 2-aminothiazole (3.29 g, 32.9 mmol) and 2-bromo-3′-cyano-acetophenone (7.37 g, 32.9 mmol) was added absolute ethanol (250 mL). The reaction was allowed to reflux with vigorous stirring for 20 hours. The reaction mixture was reduced to half its original volume in vacuo. The remaining suspension was poure...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ketone.Primary amine
null
c1cscn1
c1cn2ccsc2n1
c1ccccc1.c1cn2ccsc2n1
HBr
C(C)O
null
20
N#Cc1cccc(C(=O)CBr)c1.Nc1nccs1>C(C)O>N#Cc1cccc(-c2cn3ccsc3n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2e94214baf7e4db68f7e770b8b75e5a8
CC(=O)OC(C)=O.N#Cc1cccc(-c2cn3ccsc3n2)c1>>CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1.C(C)(=O)OC(C)=O.S(O)(O)(=O)=O>>C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C(C)=O
CC(=O)O[C:2]([CH3:1])=[O:3].[cH:4]1[c:5](-[c:6]2[cH:7][cH:8][cH:9][c:10]([C:11]#[N:12])[cH:13]2)[n:14][c:15]2[s:16][cH:17][cH:18][n:19]12>>[CH3:1][C:2](=[O:3])[c:4]1[c:5](-[c:6]2[cH:7][cH:8][cH:9][c:10]([C:11]#[N:12])[cH:13]2)[n:14][c:15]2[s:16][cH:17][cH:18][n:19]12
CC(=O)OC(C)=O.N#Cc1cccc(-c2cn3ccsc3n2)c1
CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
null
null
ClCCl
C-C Coupling
Friedel-Crafts acylation
20e4fc8dbd319e0c49a94d48e9c26d09ea69cb91c825364825442124ee99bcaa
e8c3519869b9d5fd7c4ab2911407db4a86c645fb02749ed598ab3b129e3927f8
c1ccc(-c2cn3ccsc3n2)cc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[c:4]-[c:5]1:[#7;a:6]:[c:7]2:[#16;a:8]:[c:9]:[c:10]:[#7;a:11]:2:[cH;D2;+0:12]:1>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[c;H0;D3;+0:12]1:[#7;a:11]2:[c:10]:[c:9]:[#16;a:8]:[c:7]:2:[#7;a:6]:[c:5]:1-[c:4]
74
[{"value": 74.0, "product": "C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C(C)=O", "details": "PERCENTYIELD", "is_desired": false}]
135
CELSIUS
null
null
To a mixture of 6-(3-cyanophenyl)-imidazo[2,1-b]thiazole (5.50 g, 24.4 mmol) and acetic anhydride (50 mL) was added 0.6 mL of concentrated sulfuric acid. The reaction mixture was heated at 135° C. for 5 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane (100 mL), washed with...
10.6084/m9.figshare.5104873.v1
null
Anhydride
Ketone
c1cn2ccsc2n1
c1cn2ccsc2n1
c1ccccc1.c1cn2ccsc2n1
HO-
ClCCl
135
null
CC(=O)OC(C)=O.N#Cc1cccc(-c2cn3ccsc3n2)c1>ClCCl>CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-175172ecebcc4f3781a0057d35e58ec1
CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12>>CN(C)C=CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C(C)=O>>CN(C=CC(=O)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N)C
[cH:1]1[cH:4][n:2]2[c:8]([C:6]([CH3:5])=[O:7])[c:9](-[c:10]3[cH:11][cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17]3)[n:18][c:19]2[s:20]1>>[CH3:1][N:2]([CH3:3])[CH:4]=[CH:5][C:6](=[O:7])[c:8]1[c:9](-[c:10]2[cH:11][cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17]2)[n:18][c:19]2[s:20][cH:21][cH:22][n:23]12
CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
CN(C)C=CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
null
null
COC(N(C)C)OC
Functional Group Addition
OtherReaction
d78592f81ffc52d8f66c1cf57f8590b6b3c504d4f17449a40395a3927942ea1f
6230731b070dd3e80e820430f3c2d37c21f8df4c00e299dfe083db33f2adb1d0
c1ccc(-c2cn3ccsc3n2)cc1
[CH3;D1;+0:1]-[C:2](=[O;D1;H0:3])-[c;H0;D3;+0:4]1:[c:5](-[c:6]):[#7;a:7]:[c;H0;D3;+0:8]2:[s;H0;D2;+0:9]:[cH;D2;+0:10]:[cH;D2;+0:11]:[n;H0;D3;+0:12]:2:1>>[C;D1;H3:13]-[N;H0;D3;+0:12](-[CH3;D1;+0:10])-[CH;D2;+0:11]=[CH;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c;H0;D3;+0:4]1:[#7;a:14]2:[c:15]:[c:16]:[s;H0;D2;+0:9]:[c;H0;D3;+0:8]:2:[...
null
[]
null
null
null
null
A 100 mL round bottom flask was charged with the 1-[6-(3-cyanophenyl)imidazo [2,1-b][1,3]thiazol-5-yl]ethanone (4.30 g, 16.1 mmol) and dimethylformamide dimethylacetal (40 mL). The mixture was refluxed for 6 hours and then concentrated in vacuo to provide a dark solid. LCMS: 323 [M+H]; purity: 90% by UV at 254 nm. This...
10.6084/m9.figshare.5104873.v1
null
Ketone
Enamine.Ketone
c1cn2ccsc2n1
c1cn2ccsc2n1
c1ccccc1.c1cn2ccsc2n1
Other
COC(N(C)C)OC
null
null
CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12>COC(N(C)C)OC>CN(C)C=CC(=O)c1c(-c2cccc(C#N)c2)nc2sccn12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1ccb2bec977b4fe6830c810c9bb88847
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1>>N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CN(CCC1)C(=O)OC(C)(C)C.Cl>>Cl.C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CNCCC1
CC(C)(C)OC(=O)[N:27]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:22][c:21]2[n:20][cH:19][cH:18][c:17](-[c:16]3[c:9](-[c:8]4[cH:7][cH:6][cH:5][c:4]([C:3]#[N:2])[cH:30]4)[n:10][c:11]4[s:12][cH:13][cH:14][n:15]43)[n:29]2)[CH2:28]1>>[N:2]#[C:3][c:4]1[cH:5][cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[s:12][cH:13][cH:14][n:15]3[c:16]2-[...
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
null
null
C(C)(=O)OCC
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:5]-[C:4]-[NH;D2;+0:1]-[C:2]-[C:3]
null
[]
null
null
null
null
The tert-butyl (3R)-3-({4-[6-(3-cyanophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylate (2.90 g, 5.79 mmol) was dissolved in 20 mL of ethyl acetate and treated with 30 mL of 3.0 M HCl in ethyl acetate at room temperature (RT) overnight. Solid product was filtered, washed with ethyl ace...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CCNCC1
HO-
C(C)(=O)OCC
null
null
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1>C(C)(=O)OCC>N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8779122588764ffb9c6fd39969a9d2bd
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1.O=S(=O)(Cl)c1ccc(Cl)cc1>>N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
Cl.C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CNCCC1.C(C)N(CC)CC.ClC1=CC=C(C=C1)S(=O)(=O)Cl>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N
[N:1]#[C:2][c:3]1[cH:4][cH:5][cH:6][c:7](-[c:8]2[n:9][c:10]3[s:11][cH:12][cH:13][n:14]3[c:15]2-[c:16]2[cH:17][cH:18][n:19][c:20]([NH:21][C@@H:22]3[CH2:23][CH2:24][CH2:25][NH:26][CH2:37]3)[n:38]2)[cH:39]1.Cl[S:27](=[O:28])(=[O:29])[c:30]1[cH:31][cH:32][c:33]([Cl:34])[cH:35][cH:36]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][cH:6][c...
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1.O=S(=O)(Cl)c1ccc(Cl)cc1
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
ClCCl
Miscellaneous
Sulfonamide synthesis (Schotten-Baumann) secondary amine
62fd7aa7f6e9018b348378d99729021e7cfa3bdaf0ae446bbf1fdeb2c590422b
971e620478d668662a3bf915b510f5704d42a595d6ca9c67de007bd5d7063a75
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]>>[C:7]-[C:8]-[N;H0;D3;+0:9](-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6])-[C:10]-[C:11]
97
[{"value": 97.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.5, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N", "details": "CALCULATEDPERCENTYIELD",...
null
null
1
HOUR
The 4-[6-(3-cyanophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[(3R)-piperidin-3-yl]pyrimidin-2-amine hydrochloride (˜5.79 mmol) in dichloromethane (DCM) (50 mL) was cooled to 0° C. and treated with triethylamine (4.0 mL, 28.9 mmol), then 4-chlorophenylsulfonyl chloride (1.34 g, 6.37 mmol) was added. The reaction mixture w...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
HCl
ClCCl
null
1
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1.O=S(=O)(Cl)c1ccc(Cl)cc1>ClCCl>N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-565e1347ed214a0ab82f06521329a8dd
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO>>NC(=NO)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N.Cl.NO.C([O-])([O-])=O.[Na+].[Na+]>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(N)=NO
[N:1]#[C:2][c:5]1[cH:6][cH:7][cH:8][c:9](-[c:10]2[n:11][c:12]3[s:13][cH:14][cH:15][n:16]3[c:17]2-[c:18]2[cH:19][cH:20][n:21][c:22]([NH:23][C@@H:24]3[CH2:25][CH2:26][CH2:27][N:28]([S:29](=[O:30])(=[O:31])[c:32]4[cH:33][cH:34][c:35]([Cl:36])[cH:37][cH:38]4)[CH2:39]3)[n:40]2)[cH:41]1.[NH2:3][OH:4]>>[NH2:1][C:2](=[N:3][OH:...
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO
NC(=NO)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
C(C)O.O
Heteroatom Alkylation and Arylation
Amidoxime from nitrile and hydroxylamine
5f2123b5002b6939ec57e4f55921371a47c78c3ff253c724d87881638fedcd4f
ad3f1127a4d99506976df608684863fb1e08b35faede2d4e31cf4ca96393cd2e
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5].[NH2;D1;+0:6]-[O;D1;H1:7]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[N;H0;D2;+0:6]-[O;D1;H1:7])-[c:3](:[c:4]):[c:5]
48
[{"value": 48.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(N)=NO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.7, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(N)=NO", "details": "CALCULATEDPERCEN...
80
CELSIUS
null
null
To a suspension of N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-cyano-phenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.050 g, 0.086 mmol) in 80% ethanol-water (2.5 mL) was added an aqueous solution (0.50 mL) containing 6.65 mg of hydroxylamine hydrochloride (1.1 equivalents) and 4.61 mg of sod...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
Primary amine.Oxime
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
null
C(C)O.O
80
null
N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO>C(C)O.O>NC(=NO)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae10437384e8439c99f41ed7d0798448
CO.N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>>NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
CO.ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C#N.[Br-].[Br-].[Br-].B>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N)C=CC2
C[OH:3].[N:1]#[C:2][c:4]1[cH:5][cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[s:12][cH:13][cH:14][n:15]3[c:16]2-[c:17]2[cH:18][cH:19][n:20][c:21]([NH:22][C@@H:23]3[CH2:24][CH2:25][CH2:26][N:27]([S:28](=[O:29])(=[O:30])[c:31]4[cH:32][cH:33][c:34]([Cl:35])[cH:36][cH:37]4)[CH2:38]3)[n:39]2)[cH:40]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:...
CO.N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
ClCCl
Heteroatom Alkylation and Arylation
OtherReaction
d495ded17ccf763bf499487085da685ced0129c4d8aac1f3c7a8bd356d30cdc5
061bdd0b1a0b381cc74cb84c74d6bcc8f02d1ad39972a8ccea7635f858cacf30
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
C-[OH;D1;+0:1].[N;H0;D1;+0:2]#[C;H0;D2;+0:3]-[c:4](:[c:5]):[c:6]>>[NH2;D1;+0:2]-[C;H0;D3;+0:3](=[O;H0;D1;+0:1])-[c:4](:[c:5]):[c:6]
4
[{"value": 4.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N)C=CC2", "details": "PERCENTYIELD", "is_desired": false}]
-78
CELSIUS
0.5
HOUR
To a solution of N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-cyano-phenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.50 g, 0.87 mmol) in dichloromethane (DCM) (10 mL) at −78° C. was added a solution of borane tribromide (BBr3) (1.74 mL, 1.0 M in DCM). The mixture was stirred at −78° C. for 0.5...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Methanol
Primary amide
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
Other
ClCCl
-78
0.5
CO.N#Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>ClCCl>NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6a9f8a3a7f83409f943a9a3f4b8447eb
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1.[OH-]>>CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1
C(#N)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CN(CCC1)C(=O)OC(C)(C)C.[OH-].[Na+]>>C(C)(C)(C)OC(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C(N)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][C@@H:12]([NH:13][c:14]2[n:15][cH:16][cH:17][c:18](-[c:19]3[c:20](-[c:21]4[cH:22][cH:23][cH:24][c:25]([C:26]#[N:27])[cH:29]4)[n:30][c:31]4[s:32][cH:33][cH:34][n:35]34)[n:36]2)[CH2:37]1.[OH-:28]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])...
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1.[OH-]
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1
null
null
C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
1d1793919e847ed86dcb16487e62464531560dbf4782f9a5875bfe7e0477a3ec
d6f9d146e8ef95e62f1a3ab55a7e3b4ceec8856a5f71b6dccd4ad850f945b658
c1ccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)cc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5].[OH-;D0:6]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:6])-[c:3](:[c:4]):[c:5]
83
[{"value": 83.0, "product": "C(C)(C)(C)OC(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C(N)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.7, "product": "C(C)(C)(C)OC(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C(N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desir...
75
CELSIUS
null
null
To a solution of tert-butyl (3R)-3-({4-[6-(3-cyanophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylate (0.204 g, 0.407 mmol) in ethanol (5 mL) was added 25% aqueous sodium hydroxide (0.072 mL, 0.448 mmol). The mixture was heated at 75° C. for 20 hours. Solvent was removed to dryness. Res...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amide
null
null
C1CC[NH]CC1.c1cncnc1.c1ccccc1.c1cn2ccsc2n1
null
C(C)O
75
null
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C#N)c4)nc4sccn34)n2)C1.[OH-]>C(C)O>CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d1761b5fdfe44dc7a2349407925282f7
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1>>NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
C(C)(C)(C)OC(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C(N)=O.Cl>>N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N)C=CC2
CC(C)(C)OC(=O)[N:27]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:22][c:21]2[n:20][cH:19][cH:18][c:17](-[c:16]3[c:9](-[c:8]4[cH:7][cH:6][cH:5][c:4]([C:2]([NH2:1])=[O:3])[cH:30]4)[n:10][c:11]4[s:12][cH:13][cH:14][n:15]43)[n:29]2)[CH2:28]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[s:12][cH:13][cH:1...
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1
NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
null
null
C(C)(=O)OCC
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:5]-[C:4]-[NH;D2;+0:1]-[C:2]-[C:3]
107.2
[{"value": 97.0, "product": "N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N)C=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 107.2, "product": "N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N)C=CC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
(R)-3-{4-[6-(3-carbamoyl-phenyl)-imidazo[2,1-b]thiazol-5-yl]-pyrimidin-2-ylamino}-piperidine-1-carboxylic acid tert-butyl ester (0.15 g, 0.289 mmol) was dissolved in 3 mL of ethyl acetate and treated with 3 ml of 3.0 M HCl in ethyl acetate at room temperature (RT) overnight. Solid product was filtered, washed ethyl ace...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CCNCC1
HO-
C(C)(=O)OCC
null
null
CC(C)(C)OC(=O)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C(N)=O)c4)nc4sccn34)n2)C1>C(C)(=O)OCC>NC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ed0c7b9a15ff46eca7a60f23a0d386a8
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.[OH-]>>O=C(O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N(C)OC)C=CC2.[OH-].[Li+]>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)O)C=CC2
CON(C)[C:2](=[O:1])[c:4]1[cH:5][cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[s:12][cH:13][cH:14][n:15]3[c:16]2-[c:17]2[cH:18][cH:19][n:20][c:21]([NH:22][C@@H:23]3[CH2:24][CH2:25][CH2:26][N:27]([S:28](=[O:29])(=[O:30])[c:31]4[cH:32][cH:33][c:34]([Cl:35])[cH:36][cH:37]4)[CH2:38]3)[n:39]2)[cH:40]1.[OH-:3]>>[O:1]=[C:2]([OH:3])[c:...
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.[OH-]
O=C(O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
O1CCCC1.O.CO
Acylation
OtherReaction
e4458a7867863c954d58565c6ddd87c2eeab98b7c07ecdd463e9753ebb748946
c01215fbf8824351bac42d78014a20af2990d2d56c6ce8ce9b2f77fd36798755
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[OH-;D0:6]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[OH;D1;+0:6])-[c:3](:[c:4]):[c:5]
null
[]
null
null
48
HOUR
To a solution of 3-(5-{2-[(R)-1-(4-chloro-benzenesulfonyl)-piperidin-3-ylamino]-pyrimidin-4-yl}-imidazo[2,1-b]thiazol-6-yl)-N-methoxy-N-methyl-benzamide (0.57 g, 0.089 mmol) in a mixture of methanol (1.0 mL) and tetrahydrofuran (THF) (3.0 mL) was added a solution of lithium hydroxide (0.075 g, 0.179 mmoL) in water (1.0...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Carboxylic acid
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
HO-
O1CCCC1.O.CO
null
48
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.[OH-]>O1CCCC1.O.CO>O=C(O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2f983a535bf843b38eb33d4849312b9f
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>>CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N(C)OC)C=CC2.C[Mg]Cl>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(C)=O
CON(C)[C:2](=[O:3])[c:4]1[cH:5][cH:6][cH:7][c:8](-[c:9]2[n:10][c:11]3[s:12][cH:13][cH:14][n:15]3[c:16]2-[c:17]2[cH:18][cH:19][n:20][c:21]([NH:22][C@@H:23]3[CH2:24][CH2:25][CH2:26][N:27]([S:28](=[O:29])(=[O:30])[c:31]4[cH:32][cH:33][c:34]([Cl:35])[cH:36][cH:37]4)[CH2:38]3)[n:39]2)[cH:40]1>>[CH3:1][C:2](=[O:3])[c:4]1[cH:...
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
O1CCCC1
Functional Group Interconversion
OtherReaction
0e1b501f4aadb0e84ffc93b33216cc37dfe617cb6c3e325779c58539a7f5c4e4
af85307a4412ed48cedcfde84079732215472ffbe274bdc1dc12e9979d5c5e06
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]>>[C;D1;H3:6]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
91
[{"value": 91.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(C)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 3-(5-{2-[(R)-1-(4-chloro-benzenesulfonyl)-piperidin-3-ylamino]-pyrimidin-4-yl}-imidazo[2,1-b]thiazol-6-yl)-N-methoxy-N-methyl-benzamide (0.10 g, 0.157 mmol) in anhydrous tetrahydrofuran (THF) (3.0 mL) at 0° C. was added a solution of methyl magnesium chloride (3.0 M in THF) (0.523 mL, 1.57 mmoL). The m...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Ketone
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
HO-
O1CCCC1
null
3
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>O1CCCC1>CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ffc7e0f6e2c74807b834f0c1dc768f51
CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO>>C/C(=N\O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)C(C)=O.Cl.NO.C(C)(=O)O>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)/C(/C)=N/O
O=[C:2]([CH3:1])[c:5]1[cH:6][cH:7][cH:8][c:9](-[c:10]2[n:11][c:12]3[s:13][cH:14][cH:15][n:16]3[c:17]2-[c:18]2[cH:19][cH:20][n:21][c:22]([NH:23][C@@H:24]3[CH2:25][CH2:26][CH2:27][N:28]([S:29](=[O:30])(=[O:31])[c:32]4[cH:33][cH:34][c:35]([Cl:36])[cH:37][cH:38]4)[CH2:39]3)[n:40]2)[cH:41]1.[NH2:3][OH:4]>>[CH3:1]/[C:2](=[N:...
CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO
C/C(=N\O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
ClCCl.CO
Heteroatom Alkylation and Arylation
OtherReaction
b5fd91d879f097d0ef2e8e2d3ef7d2ef0195968870a9602a47b8324c601790b9
1a0ef15294bdb221fb8888b5d4c7fcf00473b11e53da288791d32747daa48d23
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[c:3](:[c:4]):[c:5].[NH2;D1;+0:6]-[O;D1;H1:7]>>[C;D1;H3:2]/[C;H0;D3;+0:1](=[N;H0;D2;+0:6]\[O;D1;H1:7])-[c:3](:[c:4]):[c:5]
67.5
[{"value": 67.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)/C(/C)=N/O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.5, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)/C(/C)=N/O", "details": "CALCULATED...
50
CELSIUS
null
null
To a mixture of 1-(3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)ethanone (0.10 g, 0.168 mmol) and hydroxylamine hydrochloride (0.0125 g, 0.188 mmoL) in methanol (2.0 mL) was added 0.2 mL of acetic acid. The mixture was heated at 50° C. for 3 hours...
10.6084/m9.figshare.5104873.v1
null
Ketone.Primary amine
Oxime
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
HO-
ClCCl.CO
50
null
CC(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1.NO>ClCCl.CO>C/C(=N\O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4778e9adea704e30a5f454fbb8db3ba5
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>>O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C(=O)N(C)OC)C=CC2.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=O)C=CC2
CON(C)[C:2](=[O:1])[c:3]1[cH:4][cH:5][cH:6][c:7](-[c:8]2[n:9][c:10]3[s:11][cH:12][cH:13][n:14]3[c:15]2-[c:16]2[cH:17][cH:18][n:19][c:20]([NH:21][C@@H:22]3[CH2:23][CH2:24][CH2:25][N:26]([S:27](=[O:28])(=[O:29])[c:30]4[cH:31][cH:32][c:33]([Cl:34])[cH:35][cH:36]4)[CH2:37]3)[n:38]2)[cH:39]1>>[O:1]=[CH:2][c:3]1[cH:4][cH:5][...
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
null
null
O1CCCC1
Reduction
OtherReaction
1ad7fd93ee9decf7147397a16abe4237898f80cc43934fb11b6a369d0f378a48
11e681cf0fbb4d124dda7df91cf446f896c1a2472cb9bea5b83f41b090ec7b28
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
C-O-N(-C)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]>>[O;D1;H0:2]=[CH;D2;+0:1]-[c:3](:[c:4]):[c:5]
73.1
[{"value": 73.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=O)C=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 73.1, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=O)C=CC2", "details": "CALCULATEDPERCENTYIELD",...
0
CELSIUS
30
MINUTE
To a solution of 3-(5-{2-[(R)-1-(4-chloro-benzenesulfonyl)-piperidin-3-ylamino]-pyrimidin-4-yl}-imidazo[2,1-b]thiazol-6-yl)-N-methoxy-N-methyl-benzamide (0.05 g, 0.078 mmol) in anhydrous tetrahydrofuran (THF) (3.0 mL) at 0° C. was added a solution of lithium aluminum hydride (LAH) (2.0 M in THF) (0.078 mL, 0.15 mmol). ...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Aldehyde
null
null
c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CC[NH]CC1.c1ccccc1
HO-
O1CCCC1
0
0.5
CON(C)C(=O)c1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>O1CCCC1>O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fac448887d99423fbc37cb339ce21182
NO.O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>>O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C=NO)c4)nc4sccn34)n2)C1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=O)C=CC2.Cl.NO.C(C)(=O)O>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=NO)C=CC2
[NH2:30][OH:31].O=[CH:29][c:28]1[cH:27][cH:26][cH:25][c:24](-[c:23]2[c:22](-[c:21]3[cH:20][cH:19][n:18][c:17]([NH:16][C@@H:15]4[CH2:14][CH2:13][CH2:12][N:11]([S:2](=[O:1])(=[O:3])[c:4]5[cH:5][cH:6][c:7]([Cl:8])[cH:9][cH:10]5)[CH2:40]4)[n:39]3)[n:38]3[c:34]([n:33]2)[s:35][cH:36][cH:37]3)[cH:32]1>>[O:1]=[S:2](=[O:3])([c:...
NO.O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C=NO)c4)nc4sccn34)n2)C1
null
null
ClCCl.CO
Heteroatom Alkylation and Arylation
OtherReaction
26f32c058bcc6b69b34e9c38433bccb165270e0a55ab24439c783c1aee9d8dac
3593c4a8dedbac5f92a1a749cef37ecd686935362f91b9154f0c9930a5edea38
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[O;D1;H1:6]>>[O;D1;H1:6]-[N;H0;D2;+0:5]=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4]
61.3
[{"value": 61.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=NO)C=CC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.3, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=NO)C=CC2", "details": "CALCULATEDPERCENTYIELD...
50
CELSIUS
null
null
To a mixture 3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}benzaldehyde (0.81 g, 0.14 mmol) and hydroxylamine hydrochloride (0.0107 g, 0.154 mmoL) in methanol (2.0 mL) was added 0.2 mL of acetic acid. The mixture was heated at 50° C. for 2 hours. After co...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Oxime
null
null
c1ccccc1.C1CC[NH]CC1.c1cncnc1.c1ccccc1.c1cn2ccsc2n1
HO-
ClCCl.CO
50
null
NO.O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>ClCCl.CO>O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(C=NO)c4)nc4sccn34)n2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cc1c0bcfdd8d4f3bba5acc4f84a0f39d
O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>>O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(CO)c4)nc4sccn34)n2)C1
ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=O)C=CC2.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)CO
[O:1]=[S:2](=[O:3])([c:4]1[cH:5][cH:6][c:7]([Cl:8])[cH:9][cH:10]1)[N:11]1[CH2:12][CH2:13][CH2:14][C@@H:15]([NH:16][c:17]2[n:18][cH:19][cH:20][c:21](-[c:22]3[c:23](-[c:24]4[cH:25][cH:26][cH:27][c:28]([CH:29]=[O:30])[cH:31]4)[n:32][c:33]4[s:34][cH:35][cH:36][n:37]34)[n:38]2)[CH2:39]1>>[O:1]=[S:2](=[O:3])([c:4]1[cH:5][cH:...
O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1
O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(CO)c4)nc4sccn34)n2)C1
null
null
O1CCCC1
Reduction
Reduction of aldehydes and ketones to alcohols
e7895795cd3f75445716c94697823c5929dcd4b5344525875fe75d36bca2f9d7
21bb81d5469aaaca71ab12c186bea4016451717fad8780cf288858a7d8fbc55a
O=S(=O)(c1ccccc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4ccccc4)nc4sccn34)n2)C1
[O;H0;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[OH;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
71
[{"value": 71.0, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.6, "product": "ClC1=CC=C(C=C1)S(=O)(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C=2C=C(C=CC2)CO", "details": "CALCULATEDPERCENTYIELD", "...
null
null
1
HOUR
To a mixture 3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo [2,1-b][1,3]thiazol-6-yl}benzaldehyde (0.20 g, 0.346 mmol) in anhydrous tetrahydrofuran (THF) (5.0 mL) at room temperature was added a solution of lithium aluminum hydride (LAH) (2.0 M in THF) (0.346 mL, 0.692 mmol). The...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Primary alcohol
null
null
c1ccccc1.C1CC[NH]CC1.c1cncnc1.c1ccccc1.c1cn2ccsc2n1
null
O1CCCC1
null
1
O=Cc1cccc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCN(S(=O)(=O)c4ccc(Cl)cc4)C3)n2)c1>O1CCCC1>O=S(=O)(c1ccc(Cl)cc1)N1CCC[C@@H](Nc2nccc(-c3c(-c4cccc(CO)c4)nc4sccn34)n2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a248a620d0164213b25a65efa3042531
Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCN(C(=O)OC(C)(C)C)C4)n3)c2)no1>>Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCNC4)n3)c2)no1
C(C)(C)(C)OC(=O)N1C[C@@H](CCC1)NC1=NC=CC(=N1)C1=C(N=C2SC=CN21)C2=CC(=CC=C2)C2=NOC(=N2)C.Cl>>CC1=NC(=NO1)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CNCCC1
CC(C)(C)OC(=O)[N:28]1[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:23][c:22]2[n:21][cH:20][cH:19][c:18](-[c:17]3[c:10](-[c:9]4[cH:8][cH:7][cH:6][c:5](-[c:4]5[n:3][c:2]([CH3:1])[o:33][n:32]5)[cH:31]4)[n:11][c:12]4[s:13][cH:14][cH:15][n:16]43)[n:30]2)[CH2:29]1>>[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][cH:8][c:9](-[c:10]3[n:11...
Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCN(C(=O)OC(C)(C)C)C4)n3)c2)no1
Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCNC4)n3)c2)no1
null
null
C(C)(=O)OCC
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1cc(-c2ncon2)cc(-c2nc3sccn3c2-c2ccnc(N[C@@H]3CCCNC3)n2)c1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:5]-[C:4]-[NH;D2;+0:1]-[C:2]-[C:3]
109.4
[{"value": 100.0, "product": "CC1=NC(=NO1)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CNCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 109.4, "product": "CC1=NC(=NO1)C=1C=C(C=CC1)C=1N=C2SC=CN2C1C1=NC(=NC=C1)N[C@H]1CNCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
((R)-3-(4-{6-[3-(5-Methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-imidazo[2,1-b]thiazol-5-yl}-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.15 g, 0.269 mmol) was dissolved in 2 mL of ethyl acetate and treated with 2 ml of 3.0 M HCl in ethyl acetate at room temperature (RT) overnight. Solid product was fi...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ncon1.c1ccccc1.c1cn2ccsc2n1.c1cncnc1.C1CCNCC1
HO-
C(C)(=O)OCC
null
null
Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCN(C(=O)OC(C)(C)C)C4)n3)c2)no1>C(C)(=O)OCC>Cc1nc(-c2cccc(-c3nc4sccn4c3-c3ccnc(N[C@@H]4CCCNC4)n3)c2)no1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a5f349f2bfac4e1383c3b5f581edc10e
C[C@@H](CO)NC(=O)OC(C)(C)C>>C[C@@H](C=O)NC(=O)OC(C)(C)C
C(C)(C)(C)OC(=O)N[C@H](CO)C.CC(=O)OI1(C=2C=CC=CC2C(=O)O1)(OC(=O)C)OC(=O)C.S([O-])(O)=O.[Na+]>>C(C)(C)(C)OC(=O)N[C@H](C=O)C
[CH3:1][C@@H:2]([CH2:3][OH:4])[NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12]>>[CH3:1][C@@H:2]([CH:3]=[O:4])[NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12]
C[C@@H](CO)NC(=O)OC(C)(C)C
C[C@@H](C=O)NC(=O)OC(C)(C)C
null
null
C(Cl)Cl.C(C)(=O)OCC
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
null
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](=[O;D1;H0:7])-[#7:8]-[C:9](-[C;D1;H3:10])-[CH2;D2;+0:11]-[OH;D1;+0:12]>>[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](=[O;D1;H0:7])-[#7:8]-[C:9](-[C;D1;H3:10])-[CH;D2;+0:11]=[O;H0;D1;+0:12]
92
[{"value": 92.0, "product": "C(C)(C)(C)OC(=O)N[C@H](C=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.0, "product": "C(C)(C)(C)OC(=O)N[C@H](C=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
(S)-(−)-2-(tert-Butoxycarbonylamino)-1-propanol (523 mg, 2.98 mmol, 1.0 equiv.) was dissolved in 45 mL methylene chloride in a 100 mL r.b. flask with a magnetic stir bar. To this clear homogeneous solution, Dess-Martin periodinane (1.523 g, 3.591 mmol, 1.2 equiv.) was added in one portion and the cloudy white reaction ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
null
null
C(Cl)Cl.C(C)(=O)OCC
null
2
C[C@@H](CO)NC(=O)OC(C)(C)C>C(Cl)Cl.C(C)(=O)OCC>C[C@@H](C=O)NC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-890e7f96539a48dfa6ab3c51f9e65ca2
C[C@@H](CO)NC(=O)Cc1ccccc1>>C[C@@H](C=O)NC(=O)Cc1ccccc1
C(C1=CC=CC=C1)C(=O)N[C@H](CO)C.CC(=O)OI1(C=2C=CC=CC2C(=O)O1)(OC(=O)C)OC(=O)C>>C(C1=CC=CC=C1)C(=O)N[C@H](C=O)C
[CH3:1][C@@H:2]([CH2:3][OH:4])[NH:5][C:6](=[O:7])[CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[CH3:1][C@@H:2]([CH:3]=[O:4])[NH:5][C:6](=[O:7])[CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1
C[C@@H](CO)NC(=O)Cc1ccccc1
C[C@@H](C=O)NC(=O)Cc1ccccc1
null
null
C(Cl)Cl
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
c1ccccc1
[C;D1;H3:1]-[C:2](-[#7:3]-[C:4]=[O;D1;H0:5])-[CH2;D2;+0:6]-[OH;D1;+0:7]>>[C;D1;H3:1]-[C:2](-[#7:3]-[C:4]=[O;D1;H0:5])-[CH;D2;+0:6]=[O;H0;D1;+0:7]
null
[]
null
null
2
HOUR
(S)-2-(benzylcarbonylamino)-propanol (5 g, 23.9 mmol) was dissolved in CH2Cl2 (200 mL) and treated with Dess-Martin periodinane (12.26 g, 1.1 eq). The mixture was stirred for 2 hours, then quenched with sodium thiosulphate, and the solvent removed in vacuo. The residue was then separated between sodium hydroxide (1M, 5...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
c1ccccc1
null
C(Cl)Cl
null
2
C[C@@H](CO)NC(=O)Cc1ccccc1>C(Cl)Cl>C[C@@H](C=O)NC(=O)Cc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0cd77599b927482a828e3244fc616796
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)OCc1ccccc1>>C[C@H](N)CNc1ccc(OC(F)(F)F)cc1
C(C1=CC=CC=C1)OC(N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)=O>>FC(OC1=CC=C(C=C1)NC[C@H](C)N)(F)F
O=C(OCc1ccccc1)[NH:3][C@@H:2]([CH3:1])[CH2:4][NH:5][c:6]1[cH:7][cH:8][c:9]([O:10][C:11]([F:12])([F:13])[F:14])[cH:15][cH:16]1>>[CH3:1][C@H:2]([NH2:3])[CH2:4][NH:5][c:6]1[cH:7][cH:8][c:9]([O:10][C:11]([F:12])([F:13])[F:14])[cH:15][cH:16]1
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)OCc1ccccc1
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1
null
[Pd]
C(C)O
Reduction
Hydrogenolysis of amides/imides/carbamates
087b6600ba91d3df931fe6979f2445c192cbfd59e04fd2d8a10f7c7573ac669f
4e549866ec1acadec4c84aaf8495992a28ec78d8ea5ef1b9f44dd843b0dcb7d4
c1ccccc1
O=C(-O-C-c1:c:c:c:c:c:1)-[NH;D2;+0:1]-[C:2](-[C:3])-[C;D1;H3:4]>>[C:3]-[C:2](-[C;D1;H3:4])-[NH2;D1;+0:1]
72
[{"value": 72.0, "product": "FC(OC1=CC=C(C=C1)NC[C@H](C)N)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
[1-(S)-Methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-carbamic acid benzyl ester (23.9 mmol) was dissolved in ethanol (200 mL) then placed under nitrogen. 10% Palladium on carbon was added (0.5 g) and the mixture was stirred under hydrogen (atmospheric pressure) overnight. When reaction was complete, the mixture was ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
Primary amine
c1ccccc1
null
c1ccccc1
HO-
[Pd].C(C)O
null
8
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)OCc1ccccc1>[Pd].C(C)O>C[C@H](N)CNc1ccc(OC(F)(F)F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e0900b2a0fdb44c48afe1aea2bd808ca
C=C(C)CBr.CC(C)(C)OC(=O)Nc1ccc(F)cc1>>C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C
[Li]C(C)(C)C.CCCCC.C(=O)(OC(C)(C)C)NC1=CC=C(C=C1)F.C(C(C)=C)Br>>C(C)(C)(C)OC(NC1=C(C=C(C=C1)F)CC(=C)C)=O
Br[CH2:4][C:2](=[CH2:1])[CH3:3].[cH:5]1[cH:6][c:7]([F:8])[cH:9][cH:10][c:11]1[NH:12][C:13](=[O:14])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19]>>[CH2:1]=[C:2]([CH3:3])[CH2:4][c:5]1[cH:6][c:7]([F:8])[cH:9][cH:10][c:11]1[NH:12][C:13](=[O:14])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19]
C=C(C)CBr.CC(C)(C)OC(=O)Nc1ccc(F)cc1
C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C
null
null
C1CCOC1
C-C Coupling
Friedel-Crafts alkylation with halide
abd82b32c15853d5913cc8f5d51923ff8cee2c9e5cfc2628ece51b84576c3f2d
f5e5e22797736d188bba28deb76a4cee8e4fee4dca04fe24f733d2ee68a23361
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2](=[C;D1;H2:3])-[C;D1;H3:4].[C;D1;H3:5]-[C:6](-[C;D1;H3:7])(-[C;D1;H3:8])-[#8:9]-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13](:[c:14]):[cH;D2;+0:15]:[c:16]:[c:17]>>[C;D1;H2:3]=[C:2](-[C;D1;H3:4])-[CH2;D2;+0:1]-[c;H0;D3;+0:15](:[c:16]:[c:17]):[c:13](-[#7:12]-[C:10](=[O;D1;H0:11])-[#8:9]-[C:6](-[C;D1;H3:5])(...
80
[{"value": 80.0, "product": "C(C)(C)(C)OC(NC1=C(C=C(C=C1)F)CC(=C)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
-20
CELSIUS
2.5
HOUR
A solution of N-Boc-4-fluoroaniline (9.02 g, 42.7 mmol) in THF (112 mL) was cooled to −60° C. using a cryocool instrument. The solution was treated with 1.7 M t-BuLi in pentane (63 mL, 106.7 mmol) dropwise. After the first equivalent of base was consumed, a yellow solution formed. The reaction was allowed to warm to −2...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1ccccc1
c1ccccc1
c1ccccc1
HBr
C1CCOC1
-20
2.5
C=C(C)CBr.CC(C)(C)OC(=O)Nc1ccc(F)cc1>C1CCOC1>C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5c7c19b5f0cb4d9b892729fa46059a03
C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C>>CC1(C)Cc2cc(F)ccc2N1
CS(=O)(=O)O.C(C)(C)(C)OC(NC1=C(C=C(C=C1)F)CC(=C)C)=O.C1(=CC=CC=C1)OC.FC(C(=O)O)(F)F>>CC1(NC2=CC=C(C=C2C1)F)C
CC(C)(C)OC(=O)[NH:12][c:11]1[c:5]([CH2:4][C:2](=[CH2:1])[CH3:3])[cH:6][c:7]([F:8])[cH:9][cH:10]1>>[CH3:1][C:2]1([CH3:3])[CH2:4][c:5]2[cH:6][c:7]([F:8])[cH:9][cH:10][c:11]2[NH:12]1
C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C
CC1(C)Cc2cc(F)ccc2N1
null
null
ClCCl
Heteroatom Alkylation and Arylation
OtherReaction
b9db8b959ce76a9ce9ae402df8bd3b8657a4d8353a0f20fd79710a2c4e90449b
f4be2a1dc40806f7d87a3d054308bec820304200bc50fd9c846232e4d6353bb4
c1ccc2c(c1)CCN2
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]-[C:5]-[C;H0;D3;+0:6](-[C;D1;H3:7])=[CH2;D1;+0:8]>>[C;D1;H3:7]-[C;H0;D4;+0:6]1(-[CH3;D1;+0:8])-[C:5]-[c:4]:[c:2](:[c:3])-[NH;D2;+0:1]-1
66
[{"value": 66.0, "product": "CC1(NC2=CC=C(C=C2C1)F)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 65.8, "product": "CC1(NC2=CC=C(C=C2C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
170
CELSIUS
4
HOUR
A sample of [4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester (1.10 g, 4.14 mmol) was treated with anisole (5 mL), dichloromethane (5 mL) and trifluoroacetic acid (5 mL) and stirred for 4 hours. The solvent was removed and the reaction was transferred to a microwave reaction vial using methanesulfonic...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Vinyl.Boc
Secondary amine
null
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
HO-
ClCCl
170
4
C=C(C)Cc1cc(F)ccc1NC(=O)OC(C)(C)C>ClCCl>CC1(C)Cc2cc(F)ccc2N1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e1442b980ca14987bec905ca68964d5f
C=C(C)CN(C(C)=O)c1ccc(F)cc1>>CC(=O)N1CC(C)(C)c2cc(F)ccc21
FC1=CC=C(C=C1)N(C(C)=O)CC(=C)C.[Cl-].[Cl-].[Cl-].[Al+3].O>>FC=1C=C2C(CN(C2=CC1)C(C)=O)(C)C
[CH3:1][C:2](=[O:3])[N:4]([CH2:5][C:6]([CH3:7])=[CH2:8])[c:15]1[cH:9][cH:10][c:11]([F:12])[cH:13][cH:14]1>>[CH3:1][C:2](=[O:3])[N:4]1[CH2:5][C:6]([CH3:7])([CH3:8])[c:9]2[cH:10][c:11]([F:12])[cH:13][cH:14][c:15]21
C=C(C)CN(C(C)=O)c1ccc(F)cc1
CC(=O)N1CC(C)(C)c2cc(F)ccc21
null
null
C(C)(=O)OCC
C-C Coupling
OtherReaction
4d710ad3c860e47fcf3f7015a55b39b05e571ad23da36e5437a9a2523003c972
48297e5b607b4624d5b08506879ba8f9dd47fb272c10888542fa01ef83829ef2
c1ccc2c(c1)CCN2
[C;D1;H3:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5]-[C;H0;D3;+0:6](-[C;D1;H3:7])=[CH2;D1;+0:8])-[c:9](:[c:10]):[cH;D2;+0:11]:[c:12]:[c:13]>>[C;D1;H3:1]-[C:2](=[O;D1;H0:3])-[#7:4]1-[C:5]-[C;H0;D4;+0:6](-[C;D1;H3:7])(-[CH3;D1;+0:8])-[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:9]-1:[c:10]
null
[]
150
CELSIUS
null
null
According to the procedure described in S. Coulton et al. WO9925709 with the following modifications. N-(4-Fluoro-phenyl)-N-(2-methyl-allyl)-acetamide (5 grams, 24.12 mmol) was added to a microwave tube with aluminum trichloride (7 grams, 52.4 mmol). The tube was capped and heated to 150° C. for 20 minutes under microw...
10.6084/m9.figshare.5104873.v1
null
Vinyl
null
c1ccccc1
c1ccc2c(c1)CC[NH]2
c1ccc2c(c1)CC[NH]2
null
C(C)(=O)OCC
150
null
C=C(C)CN(C(C)=O)c1ccc(F)cc1>C(C)(=O)OCC>CC(=O)N1CC(C)(C)c2cc(F)ccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-93a099c3483445ae9df313c7ccd83d5c
CC(=O)N1CC(C)(C)c2cc(F)ccc21>>CC1(C)CNc2ccc(F)cc21
FC=1C=C2C(CN(C2=CC1)C(C)=O)(C)C>>CC1(CNC2=CC=C(C=C12)F)C
CC(=O)[N:5]1[CH2:4][C:2]([CH3:1])([CH3:3])[c:12]2[c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11]2>>[CH3:1][C:2]1([CH3:3])[CH2:4][NH:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][c:12]21
CC(=O)N1CC(C)(C)c2cc(F)ccc21
CC1(C)CNc2ccc(F)cc21
null
null
Cl
Reduction
Hydrogenolysis of tertiary amines
3325d321b6e740eb07332b61ecb10184cad4db5efbb86509e39d17e13b7f3d02
62cf08a8ae6315067a063b5b3495125ccbdaff6b2340ce1d3e1c7b6cde962ae4
c1ccc2c(c1)CCN2
C-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[c:4]:[c:5]-1:[c:6]>>[c:6]:[c:5]1:[c:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
200
CELSIUS
null
null
According to the procedure described in S. Coulton et al. WO9925709 with the following modifications. N-(4-Fluoro-phenyl)-N-(2-methyl-allyl)-acetamide (5 grams, 24.12 mmol) was added to a microwave tube with aluminum trichloride (7 grams, 52.4 mmol). The tube was capped and heated to 150° C. for 20 minutes under microw...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Secondary amine
c1ccc2c(c1)CC[NH]2
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
HO-
Cl
200
null
CC(=O)N1CC(C)(C)c2cc(F)ccc21>Cl>CC1(C)CNc2ccc(F)cc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4a688b44877b428d8a89c050175e0a95
O=C(N[C@H](C(=O)O)C1CC1)OCc1ccccc1>>O=C(N[C@H](CO)C1CC1)OCc1ccccc1
C(C1=CC=CC=C1)OC(=O)N[C@H](C(=O)O)C1CC1.Cl>>C(C1=CC=CC=C1)OC(N[C@H](CO)C1CC1)=O
O=[C:5]([C@@H:4]([NH:3][C:2](=[O:1])[O:10][CH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1)[CH:7]1[CH2:8][CH2:9]1)[OH:6]>>[O:1]=[C:2]([NH:3][C@H:4]([CH2:5][OH:6])[CH:7]1[CH2:8][CH2:9]1)[O:10][CH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1
O=C(N[C@H](C(=O)O)C1CC1)OCc1ccccc1
O=C(N[C@H](CO)C1CC1)OCc1ccccc1
null
null
C1CCOC1
Reduction
Reduction of carboxylic acid to primary alcohol
0db83a5ebe1e318b78b55461cf7eb8f7c004eef0f9e3b6666d3df4c96b5f665e
93b4621647b04d2ad2f2825215b1567f171ba61fe10d136b5db6ea0470aa4932
O=C(NCC1CC1)OCc1ccccc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[C:3](-[C:4])-[#7:5]-[C:6]=[O;D1;H0:7]>>[C:4]-[C:3](-[#7:5]-[C:6]=[O;D1;H0:7])-[CH2;D2;+0:1]-[O;D1;H1:2]
50
[{"value": 50.0, "product": "C(C1=CC=CC=C1)OC(N[C@H](CO)C1CC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.8, "product": "C(C1=CC=CC=C1)OC(N[C@H](CO)C1CC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
A solution of (S)-benzyloxycarbonylamino-cyclopropyl-acetic acid (3.2 g, 12.8 mmol) in THF (20 mL) was cooled in an ice/water bath and treated with a 1 M solution of BH3 in THF (16.7 mL, 16.7 mmol). The reaction was stirred for 4 hours and then treated with 1 M HCl until the bubbling ceased. The reaction was stirred ov...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary alcohol
null
null
C1CC1.c1ccccc1
Other
C1CCOC1
null
4
O=C(N[C@H](C(=O)O)C1CC1)OCc1ccccc1>C1CCOC1>O=C(N[C@H](CO)C1CC1)OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fad66d30e14f4e2597d7628ec4bb0ca3
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O>>COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
FC=1C=C2C(C(NC2=CC1)=O)=O.[H-].[Na+].COC1=CC=C(CCl)C=C1>>FC=1C=C2C(C(N(C2=CC1)CC1=CC=C(C=C1)OC)=O)=O
Cl[CH2:7][c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:21][cH:20]1.[NH:8]1[C:9](=[O:10])[C:11](=[O:12])[c:13]2[cH:14][c:15]([F:16])[cH:17][cH:18][c:19]21>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][N:8]2[C:9](=[O:10])[C:11](=[O:12])[c:13]3[cH:14][c:15]([F:16])[cH:17][cH:18][c:19]32)[cH:20][cH:21]1
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O
COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
c168ddb7803c893ec5334f16b8c2262b487eff0908e05ac9b9feab6bfceb9bd3
4a6c1e88c9e8bed487b746792f88d478ff36cc235f9a217d4632e6babdebdc9a
O=C1C(=O)N(Cc2ccccc2)c2ccccc21
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]-1=[O;D1;H0:12]>>[O;D1;H0:5]=[C:6]1-[C:11](=[O;D1;H0:12])-[c:10]:[c:8](:[c:9])-[N;H0;D3;+0:7]-1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
82.4
[{"value": 82.0, "product": "FC=1C=C2C(C(N(C2=CC1)CC1=CC=C(C=C1)OC)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.4, "product": "FC=1C=C2C(C(N(C2=CC1)CC1=CC=C(C=C1)OC)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
A solution of 5-fluoroisatin (5 g, 30.2 mmol) in DMF (60 mL) was cooled in an ice/water bath and treated with sodium hydride (1.44 g, 60.6 mmol) portionwise. The reaction was stirred for 15 minutes after the addition of the last portion and then treated with p-methoxybenzyl chloride (5.32 g, 45.3 mmol) and allowed to s...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Tertiary amide
c1ccc2c(c1)CCN2
c1ccc2c(c1)CC[NH]2
c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl
CN(C)C=O
null
0.25
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O>CN(C)C=O>COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-90138d8dc9d84d73ad6048fe33ec7bc8
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O>>COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
O.FC=1C=C2C(C(NC2=CC1)=O)=O.[H-].[Na+].COC1=CC=C(CCl)C=C1>>FC=1C=C2C(C(N(C2=CC1)CC1=CC=C(C=C1)OC)=O)=O
Cl[CH2:7][c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:21][cH:20]1.[NH:8]1[C:9](=[O:10])[C:11](=[O:12])[c:13]2[cH:14][c:15]([F:16])[cH:17][cH:18][c:19]21>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][N:8]2[C:9](=[O:10])[C:11](=[O:12])[c:13]3[cH:14][c:15]([F:16])[cH:17][cH:18][c:19]32)[cH:20][cH:21]1
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O
COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
null
null
C(C)(=O)OCC.CCCCCC.CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
c168ddb7803c893ec5334f16b8c2262b487eff0908e05ac9b9feab6bfceb9bd3
4a6c1e88c9e8bed487b746792f88d478ff36cc235f9a217d4632e6babdebdc9a
O=C1C(=O)N(Cc2ccccc2)c2ccccc21
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]-[C:11]-1=[O;D1;H0:12]>>[O;D1;H0:5]=[C:6]1-[C:11](=[O;D1;H0:12])-[c:10]:[c:8](:[c:9])-[N;H0;D3;+0:7]-1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
80
[{"value": 80.0, "product": "FC=1C=C2C(C(N(C2=CC1)CC1=CC=C(C=C1)OC)=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
5-Fluoro-1H-indole-2,3-dione (956 mg, 5.79 mmol, 1 eq) was added as a solution in dry DMF to a stirred slurry of sodium hydride (278 mg, 11.6 mmol, 2 eq) in dry DMF drop wise over 15 minutes under an inert atmosphere with adequate pressure release to accommodate H2 evolution. The resulting mixture was stirred for 1 hou...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Tertiary amide
c1ccc2c(c1)CCN2
c1ccc2c(c1)CC[NH]2
c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl
C(C)(=O)OCC.CCCCCC.CN(C)C=O
null
0.25
COc1ccc(CCl)cc1.O=C1Nc2ccc(F)cc2C1=O>C(C)(=O)OCC.CCCCCC.CN(C)C=O>COc1ccc(CN2C(=O)C(=O)c3cc(F)ccc32)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3d2bf968e38a48499b840bebcf57db85
C[C@@](O)(C(=O)O)C1CCCCC1.NCCN1CCc2cc(F)ccc21>>O=C(NCCN1CCc2cc(F)ccc21)[C@@H](O)CC1CCCCC1
C1(CCCCC1)[C@@](C(=O)O)(O)C.FC=1C=C2CCN(C2=CC1)CCN.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>C1(CCCCC1)C[C@@H](C(=O)NCCN1CCC2=CC(=CC=C12)F)O
O[C:2](=[O:1])[C@:16]([OH:17])([CH3:18])[CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1.[NH2:3][CH2:4][CH2:5][N:6]1[CH2:7][CH2:8][c:9]2[cH:10][c:11]([F:12])[cH:13][cH:14][c:15]21>>[O:1]=[C:2]([NH:3][CH2:4][CH2:5][N:6]1[CH2:7][CH2:8][c:9]2[cH:10][c:11]([F:12])[cH:13][cH:14][c:15]21)[C@@H:16]([OH:17])[CH2:18][CH:19]1[C...
C[C@@](O)(C(=O)O)C1CCCCC1.NCCN1CCc2cc(F)ccc21
O=C(NCCN1CCc2cc(F)ccc21)[C@@H](O)CC1CCCCC1
null
null
C(Cl)Cl.C(C)(=O)OCC
Acylation
OtherReaction
8b5cce7e7b144073d5b05dd864ab1077165b109863da7ae2850d3790f9ed42d5
315769563e8b03437a63a4166d6856a701ea134077d01ad7d2e966fdc1d17f39
O=C(CCC1CCCCC1)NCCN1CCc2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C@@;H0;D4;+0:3](-[CH3;D1;+0:4])(-[O;D1;H1:5])-[CH;D3;+0:6](-[C:7]-[C:8])-[C:9]-[C:10].[C:11]-[C:12]-[NH2;D1;+0:13]>>[C:8]-[C:7]-[CH;D3;+0:6](-[CH2;D2;+0:4]-[C@H;D3;+0:3](-[O;D1;H1:5])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:13]-[C:12]-[C:11])-[C:9]-[C:10]
28
[{"value": 28.0, "product": "C1(CCCCC1)C[C@@H](C(=O)NCCN1CCC2=CC(=CC=C12)F)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a stirring suspension of (S)-cyclohexyl lactic acid (558 mg, 3.42 mmol) in CH2Cl2 was added 2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylamine (616 mg, 3.42 mmol), HATU (1.429 g, 3.76 mmol), and DIEA (1.79 mL, 10.3 mmol). The reaction mixture was stirred at room temperature for several hours until the starting material ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Tertiary alcohol.Primary amine
Secondary amide.Secondary alcohol
C1CCCCC1
C1CCCCC1
c1ccc2c(c1)CC[NH]2.C1CCCCC1
HO-
C(Cl)Cl.C(C)(=O)OCC
null
null
C[C@@](O)(C(=O)O)C1CCCCC1.NCCN1CCc2cc(F)ccc21>C(Cl)Cl.C(C)(=O)OCC>O=C(NCCN1CCc2cc(F)ccc21)[C@@H](O)CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f869eb9b164c4cca94362b68c0e38e8d
COC(=O)[C@@H](CC(=O)O)CC1CCCCC1.NCCNc1ccc(F)cc1>>COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1
COC([C@@H](CC(=O)O)CC1CCCCC1)=O.C(C)(C)N(CC)C(C)C.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.FC1=CC=C(C=C1)NCCN>>COC([C@@H](CC(=O)NCCNC1=CC=C(C=C1)F)CC1CCCCC1)=O
O[C:7]([CH2:6][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:20][CH:21]1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1)=[O:8].[NH2:9][CH2:10][CH2:11][NH:12][c:13]1[cH:14][cH:15][c:16]([F:17])[cH:18][cH:19]1>>[CH3:1][O:2][C:3](=[O:4])[C@@H:5]([CH2:6][C:7](=[O:8])[NH:9][CH2:10][CH2:11][NH:12][c:13]1[cH:14][cH:15][c:16]([F:17])[cH:18]...
COC(=O)[C@@H](CC(=O)O)CC1CCCCC1.NCCNc1ccc(F)cc1
COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1
null
null
ClCCl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(CCCC1CCCCC1)NCCNc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C:5](-[#8:6])=[O;D1;H0:7].[C:8]-[C:9]-[NH2;D1;+0:10]>>[#8:6]-[C:5](=[O;D1;H0:7])-[C:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[C:9]-[C:8]
65
[{"value": 65.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
(R)-2-(Cyclohexylmethyl)succinic acid-1-methyl ester (211 mg, 0.93 mmol) from Acros Organics was treated with (500 μL, 2.87 mmol, 3.1 eq.) of diisopropylethylamine, HATU (360 mg, 1.096 mmol, 1.2 eq.) and (N-(4-Fluoro-phenyl)-ethane-1,2-diamine) (210 mg, 0.93 mmol, 1 eq.). The reagents were dissolved in dry dichlorometh...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.C1CCCCC1
HO-
ClCCl
null
5
COC(=O)[C@@H](CC(=O)O)CC1CCCCC1.NCCNc1ccc(F)cc1>ClCCl>COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d0407a9318944a7e917dcccb34ff3fef
COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1>>O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1
COC([C@@H](CC(=O)NCCNC1=CC=C(C=C1)F)CC1CCCCC1)=O.[OH-].[Li+]>>C1(CCCCC1)C[C@@H](C(=O)O)CC(=O)NCCNC1=CC=C(C=C1)F
C[O:14][C:12]([C@@H:4]([CH2:3][C:2](=[O:1])[NH:15][CH2:16][CH2:17][NH:18][c:19]1[cH:20][cH:21][c:22]([F:23])[cH:24][cH:25]1)[CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:13]>>[O:1]=[C:2]([CH2:3][C@@H:4]([CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)[C:12](=[O:13])[OH:14])[NH:15][CH2:16][CH2:17][NH:18]...
COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1
O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1
null
null
O.CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(CCCC1CCCCC1)NCCNc1ccccc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
86
[{"value": 86.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
23
CELSIUS
8
HOUR
(R)-2-cyclohexylmethyl-N-[2-(4-fluoro-phenylamino)-ethyl]-succinamic acid methyl ester (220 mg, 0.60 mmol, 1.0 eq.) was dissolved in a mixture of MeOH (4.5 mL) and H2O (3 mL) and placed in a 0° C. ice bath. Lithium hydroxide (30 mg, 1.25 mmol, 2.1 eq.) was added in one portion and allowed to stir for 8 hours, slowly wa...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CCCCC1.c1ccccc1
Other
O.CO
23
8
COC(=O)[C@@H](CC(=O)NCCNc1ccc(F)cc1)CC1CCCCC1>O.CO>O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5577055f2f0042359bf67e6684fc6dd9
C1COCCN1.O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1>>O=C(C[C@@H](CC1CCCCC1)C(=O)N1CCOCC1)NCCNc1ccc(F)cc1
C(C)(C)N(CC)C(C)C.C1(CCCCC1)C[C@@H](C(=O)O)CC(=O)NCCNC1=CC=C(C=C1)F.N1CCOCC1.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F>>C1(CCCCC1)C[C@H](CC(=O)NCCNC1=CC=C(C=C1)F)C(=O)N1CCOCC1
[NH:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1.O[C:12]([C@@H:4]([CH2:3][C:2](=[O:1])[NH:20][CH2:21][CH2:22][NH:23][c:24]1[cH:25][cH:26][c:27]([F:28])[cH:29][cH:30]1)[CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:13]>>[O:1]=[C:2]([CH2:3][C@@H:4]([CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)[C:12](=[O:...
C1COCCN1.O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1
O=C(C[C@@H](CC1CCCCC1)C(=O)N1CCOCC1)NCCNc1ccc(F)cc1
null
null
ClCCl
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
2ef483949e7ba3e5f888cf14cdce25fa611f75be09fdf1854a473be519821b59
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(C[C@@H](CC1CCCCC1)C(=O)N1CCOCC1)NCCNc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]-[C:6](-[#7:7])=[O;D1;H0:8].[#8:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[#7:7]-[C:6](=[O;D1;H0:8])-[C:5]-[C:3](-[C:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:12]1-[C:11]-[C:10]-[#8:9]-[C:14]-[C:13]-1
48.1
[{"value": 40.0, "product": "C1(CCCCC1)C[C@H](CC(=O)NCCNC1=CC=C(C=C1)F)C(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.1, "product": "C1(CCCCC1)C[C@H](CC(=O)NCCNC1=CC=C(C=C1)F)C(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
(R)-2-cyclohexylmethyl-N-[2-(4-fluoro-phenylamino)-ethyl]-succinamic acid (220 mg, 0.52 mmol) was treated with morpholine (110 μL, 1.26 mmol, 2.4 eq.) and HATU (238 mg, 0.72 mmol, 1.4 eq.). The reagents were dissolved in dry dichloromethane (4 mL) and treated with diisopropylethylamine (315 μL, 1.81 mmol, 3.5 eq.). The...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1COCCN1
C1COCC[NH]1
C1CCCCC1.C1COCC[NH]1.c1ccccc1
HO-
ClCCl
null
null
C1COCCN1.O=C(C[C@@H](CC1CCCCC1)C(=O)O)NCCNc1ccc(F)cc1>ClCCl>O=C(C[C@@H](CC1CCCCC1)C(=O)N1CCOCC1)NCCNc1ccc(F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6a83582ae7f04490a5d77f1c027da962
O=C(N[C@@H](COCc1ccccc1)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1>>O=C(N[C@@H](CO)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1
C1(CCCCC1)C[C@@H](C(=O)N1CCOCC1)OC(N[C@H](CN1CCC2=CC(=CC=C12)F)COCC1=CC=CC=C1)=O>>C1(CCCCC1)C[C@@H](C(=O)N1CCOCC1)OC(N[C@H](CN1CCC2=CC(=CC=C12)F)CO)=O
c1ccc(C[O:6][CH2:5][C@H:4]([NH:3][C:2](=[O:1])[O:18][C@@H:19]([CH2:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]2)[C:27](=[O:28])[N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)[CH2:7][N:8]2[CH2:9][CH2:10][c:11]3[cH:12][c:13]([F:14])[cH:15][cH:16][c:17]32)cc1>>[O:1]=[C:2]([NH:3][C@@H:4]([CH2:5][OH:6])[CH2:7][N:8]1...
O=C(N[C@@H](COCc1ccccc1)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1
O=C(N[C@@H](CO)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1
null
[Pd]
CO
Deprotection
Hydroxyl benzyl deprotection
c8a6fd2e05b2d36256c76b73aaf4118f20eb14abce1c0289b554265e30b218aa
29a81fd08d26edc3da6d72c4958026f5af2119326dc1b4714ee5be1c41835609
O=C(NCCN1CCc2ccccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1
[C:1]-[C:2]-[O;H0;D2;+0:3]-C-c1:c:c:c:c:c:1>>[C:1]-[C:2]-[OH;D1;+0:3]
71.4
[{"value": 71.0, "product": "C1(CCCCC1)C[C@@H](C(=O)N1CCOCC1)OC(N[C@H](CN1CCC2=CC(=CC=C12)F)CO)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.4, "product": "C1(CCCCC1)C[C@@H](C(=O)N1CCOCC1)OC(N[C@H](CN1CCC2=CC(=CC=C12)F)CO)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound of Example 10 (50 mg, 0.088 mmol) was dissolved in a minimum amount of methanol (approx. 1-2 mL) and a catalytic amount of 10% Pd/C was added. Air was purged from the reaction vessel and H2 gas was introduced via a balloon. The reaction mixture was stirred for several hours under a H2 atmosphere, aft...
10.6084/m9.figshare.5104873.v1
null
Ether
Primary alcohol
c1ccccc1
null
c1ccc2c(c1)CC[NH]2.C1CCCCC1.C1COCC[NH]1
Other
[Pd].CO
null
null
O=C(N[C@@H](COCc1ccccc1)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1>[Pd].CO>O=C(N[C@@H](CO)CN1CCc2cc(F)ccc21)O[C@@H](CC1CCCCC1)C(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-51a95571010e457c8778b0219e6c730d
CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1.OO>>CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)O
OO.[Li+].[OH-].C(C)(C)(C)OC(C[C@H](C(=O)N1C(OC[C@@H]1CC1=CC=CC=C1)=O)CC1CCCC1)=O.S(=O)([O-])[O-].[Na+].[Na+].C([O-])(O)=O.[Na+]>>C(C)(C)(C)OC(C[C@H](C(=O)O)CC1CCCC1)=O
O=C1OC[C@H](Cc2ccccc2)N1[C:16]([C@@H:9]([CH2:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)=[O:17].O[OH:18]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[CH2:8][C@@H:9]([CH2:10][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)[C:16](=[O:17])[OH:18]
CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1.OO
CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)O
null
null
O.C1CCOC1
Protection
OtherReaction
5e8d363a37fc08652d7428d883ecf869fb4ee2b7eef0b3e6daf3598f9da8bd9f
c56e1872d5846fe1c198ecc1bf4849e80e217897fb667d1c951e7cecf0d4c289
C1CCCC1
O-[OH;D1;+0:1].O=C1-O-C-[C@H](-C-c2:c:c:c:c:c:2)-N-1-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4](-[C:5])-[C:6]-[C:7](-[#8:8])=[O;D1;H0:9]>>[#8:8]-[C:7](=[O;D1;H0:9])-[C:6]-[C:4](-[C:5])-[C;H0;D3;+0:2](=[O;D1;H0:3])-[OH;D1;+0:1]
73
[{"value": 73.0, "product": "C(C)(C)(C)OC(C[C@H](C(=O)O)CC1CCCC1)=O", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
4-(4-(S)-Benzyl-2-oxo-oxazolidin-3-yl)-3-(R)-cyclopentylmethyl-4-oxo-butyric acid tert-butyl ester (620 mg, 1.49 mmol, 1.0 eq.) was dissolved in THF (35 mL) and cooled in a 0° C. ice-water bath. Hydrogen peroxide (31 w/w %) (654 μL, 5.97 mmol, 4.0 eq.) and LiOH (72 mg, 2.98 mmol, 2.0 eq.) in water (7.5 mL) was added to...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Substituted dicarboximide.Peroxide
Carboxylic acid
C1COCN1.c1ccccc1
null
C1CCCC1
HO-
O.C1CCOC1
0
null
CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1.OO>O.C1CCOC1>CC(C)(C)OC(=O)C[C@@H](CC1CCCC1)C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1cc77382802c48728c4db5a5d524e272
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1>>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1
CCN(C(C)C)C(C)C.C(C1=CC=CC=C1)SC[C@@H](C(=O)O)NC(=O)N1CCOCC1.FC(OC1=CC=C(C=C1)NC[C@H](C)N)(F)F.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F>>C(C1=CC=CC=C1)SC[C@@H](C(N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)=O)NC(=O)N1CCOCC1
[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7][c:8]([O:9][C:10]([F:11])([F:12])[F:13])[cH:14][cH:15]1)[NH2:16].O[C:17](=[O:18])[C@H:19]([CH2:20][S:21][CH2:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1)[NH:29][C:30](=[O:31])[N:32]1[CH2:33][CH2:34][O:35][CH2:36][CH2:37]1>>[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7]...
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1
null
null
C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCNc1ccccc1)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5]-[C:6]=[O;D1;H0:7].[C:8]-[C:9](-[C;D1;H3:10])-[NH2;D1;+0:11]>>[C:4]-[C:3](-[#7:5]-[C:6]=[O;D1;H0:7])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:11]-[C:9](-[C:8])-[C;D1;H3:10]
6.4
[{"value": 5.0, "product": "C(C1=CC=CC=C1)SC[C@@H](C(N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)=O)NC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 6.4, "product": "C(C1=CC=CC=C1)SC[C@@H](C(N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)=O)NC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Benzylsulfanyl-2-(R)-[(morpholine-4-carbonyl)-amino]-propionic acid (182 mg, 0.56 mmol, 1.2 eq.), N1-(4-Trifluoromethoxy-phenyl)-(S)-propane-1,2-diamine from Scheme 1a (110 mg, 0.47 mmol, 1.0 eq.), and HATU (185 mg, 0.56 mmol, 1.2 eq.) were dissolved in CH2Cl2 (2 mL) at room temperature. DIPEA (245 μL, 1.41 mmol, 3.0...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.C1COCC[NH]1
HO-
C(Cl)Cl
null
null
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1>C(Cl)Cl>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CSCc1ccccc1)NC(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b03582c0106445d5969ece8a2d778f3b
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1>>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1
N1(CCOCC1)C(=O)N[C@H](C(=O)O)CS(=O)(=O)CC1=CC=CC=C1.FC(OC1=CC=C(C=C1)NC[C@H](C)N)(F)F.C(CCl)Cl.C=1C=CC2=C(C1)N=NN2O.CN1CCOCC1>>C[C@@H](CNC1=CC=C(C=C1)OC(F)(F)F)NC(=O)[C@H](CS(=O)(=O)CC1=CC=CC=C1)NC(=O)N1CCOCC1
[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7][c:8]([O:9][C:10]([F:11])([F:12])[F:13])[cH:14][cH:15]1)[NH2:16].O[C:17](=[O:18])[C@H:19]([CH2:20][S:21](=[O:22])(=[O:23])[CH2:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1)[NH:31][C:32](=[O:33])[N:34]1[CH2:35][CH2:36][O:37][CH2:38][CH2:39]1>>[CH3:1][C@@H:2]([CH2:3][NH:4]...
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1
null
null
C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCNc1ccccc1)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5]-[C:6]=[O;D1;H0:7].[C:8]-[C:9](-[C;D1;H3:10])-[NH2;D1;+0:11]>>[C:4]-[C:3](-[#7:5]-[C:6]=[O;D1;H0:7])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:11]-[C:9](-[C:8])-[C;D1;H3:10]
31
[{"value": 31.0, "product": "C[C@@H](CNC1=CC=C(C=C1)OC(F)(F)F)NC(=O)[C@H](CS(=O)(=O)CC1=CC=CC=C1)NC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 28.6, "product": "C[C@@H](CNC1=CC=C(C=C1)OC(F)(F)F)NC(=O)[C@H](CS(=O)(=O)CC1=CC=CC=C1)NC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_des...
null
null
null
null
2-(R)-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (73 mg, 0.21 mmol, 1.0 eq.), N1-(4-Trifluoromethoxy-phenyl)-(S)-propane-1,2-diamine from Scheme 1a (48 mg, 0.21 mmol, 1.0 eq.), EDC (59 mg, 0.31 mmol, 1.5 eq.), and HOBT (38 mg, 0.25 mmol, 1.2 eq.) were dissolved in CH2Cl2 at room temperature....
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.C1COCC[NH]1
HO-
C(Cl)Cl
null
null
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1>C(Cl)Cl>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CS(=O)(=O)Cc1ccccc1)NC(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8d58f29af60b4591908b70035a518ec4
CC(C)(C)OC(=O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1>>O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
C(C)(C)(C)OC(C[C@@H](CCC1CCCCC1)C(=O)N1C(OC[C@@H]1CC1=CC=CC=C1)=O)=O.C(Cl)Cl.C(=O)(C(F)(F)F)O>>C(C1=CC=CC=C1)[C@@H]1N(C(OC1)=O)C(=O)[C@@H](CC(=O)O)CCC1CCCCC1
CC(C)(C)[O:3][C:2](=[O:1])[CH2:4][C@@H:5]([CH2:6][CH2:7][CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)[C:14](=[O:15])[N:16]1[C:17](=[O:18])[O:19][CH2:20][C@@H:21]1[CH2:22][c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1>>[O:1]=[C:2]([OH:3])[CH2:4][C@@H:5]([CH2:6][CH2:7][CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)[C:14...
CC(C)(C)OC(=O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
null
null
O
Deprotection
Deprotection of carboxylic acid
152e5537e48c95b4a3e767536b0f9f68d1308e5f484070828ab5ed951805157a
7f019d4cfe9b3036d0a2d3a3209aa0e1fcb05418ebee15a4be5e125d315d5f01
O=C(CCCC1CCCCC1)N1C(=O)OC[C@@H]1Cc1ccccc1
C-C(-C)(-C)-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
null
null
1
HOUR
3-(R)-(4-(S)-Benzyl-2-oxo-oxazolidine-3-carbonyl)-5-cyclohexyl-pentanoic acid tert-butyl ester (2.01 g, 4.53 mmol, 1.0 eq) was treated with a 45:50:5 CH2Cl2:TFA:H2O solution. The reaction was monitored by LC/MS and complete after 1 hour. The solution was evaporated and provided a quantitative yield of 3-(R)-(4-(S)-Benz...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid
null
null
C1CCCCC1.C1COC[NH]1.c1ccccc1
Other
O
null
1
CC(C)(C)OC(=O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1>O>O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f9dba20689f8425caa177133c2210e82
C1COCCN1.O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1>>O=C(C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)N1CCOCC1
N1CCOCC1.C(C1=CC=CC=C1)[C@@H]1N(C(OC1)=O)C(=O)[C@@H](CC(=O)O)CCC1CCCCC1.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.N1CCOCC1.CCN(C(C)C)C(C)C>>C(C1=CC=CC=C1)[C@@H]1N(C(OC1)=O)C([C@@H](CC(=O)N1CCOCC1)CCC1CCCCC1)=O
[NH:28]1[CH2:29][CH2:30][O:31][CH2:32][CH2:33]1.O[C:2](=[O:1])[CH2:3][C@@H:4]([CH2:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1)[C:13](=[O:14])[N:15]1[C:16](=[O:17])[O:18][CH2:19][C@@H:20]1[CH2:21][c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1>>[O:1]=[C:2]([CH2:3][C@@H:4]([CH2:5][CH2:6][CH:7]1[CH2:8][CH2:9][CH2...
C1COCCN1.O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
O=C(C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)N1CCOCC1
null
null
CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
2ef483949e7ba3e5f888cf14cdce25fa611f75be09fdf1854a473be519821b59
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C:5](-[#7:6])=[O;D1;H0:7].[#8:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-[C:13]-1>>[#7:6]-[C:5](=[O;D1;H0:7])-[C:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[#8:8]-[C:13]-[C:12]-1
92.3
[{"value": 92.0, "product": "C(C1=CC=CC=C1)[C@@H]1N(C(OC1)=O)C([C@@H](CC(=O)N1CCOCC1)CCC1CCCCC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.3, "product": "C(C1=CC=CC=C1)[C@@H]1N(C(OC1)=O)C([C@@H](CC(=O)N1CCOCC1)CCC1CCCCC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
3-(R)-(4-(S)-Benzyl-2-oxo-oxazolidine-3-carbonyl)-5-cyclohexyl-pentanoic acid (1.76 g, 4.53 mmol, 1.0 eq.) dissolved in DMF (10 mL) and treated with HATU (1.3 g, 5.0 mmol, 1.1 eq.), morpholine (680 μL, 7.77 mmol, 1.7 eq.) and DIPEA (870 μL, 5.0 mmol, 1.1 eq.). Alternatively an additional equivalent of morpholine can be...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1COCCN1
C1COCC[NH]1
C1CCCCC1.C1COC[NH]1.c1ccccc1.C1COCC[NH]1
HO-
CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC
null
null
C1COCCN1.O=C(O)C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1>CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC>O=C(C[C@@H](CCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c73d7984a4e44da3b5dfa3e104d5e889
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1>>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1
C1(CCCCC1)CC[C@@H](C(=O)O)CC(=O)N1CCOCC1.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.FC(OC1=CC=C(C=C1)NC[C@H](C)N)(F)F.CCN(C(C)C)C(C)C>>C1(CCCCC1)CC[C@@H](C(=O)N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)CC(=O)N1CCOCC1
[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7][c:8]([O:9][C:10]([F:11])([F:12])[F:13])[cH:14][cH:15]1)[NH2:16].O[C:17](=[O:18])[C@H:19]([CH2:20][CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1)[CH2:28][C:29](=[O:30])[N:31]1[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1>>[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7...
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1
null
null
CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCNc1ccccc1)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]-[C:6](-[#7:7])=[O;D1;H0:8].[C:9]-[C:10](-[C;D1;H3:11])-[NH2;D1;+0:12]>>[#7:7]-[C:6](=[O;D1;H0:8])-[C:5]-[C:3](-[C:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:12]-[C:10](-[C:9])-[C;D1;H3:11]
null
[]
null
null
null
null
2-(R)-(2-Cyclohexyl-ethyl)-4-morpholin-4-yl-4-oxo-butyric acid (98 mg, 0.33 mmol, 1.0 eq.) dissolved in DMF (2 mL) and treated with HATU (137 mg, 0.36 mmol, 1.1 eq.), (S)—N1-(4-Trifluoromethoxy-phenyl)-propane-1,2-diamine (85 mg, 0.36 mmol, 1.1 eq.) and DIPEA (63 μL, 0.36 mmol, 1.1 eq.). Alternatively CH2Cl2 can be use...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.C1CCCCC1.C1COCC[NH]1
HO-
CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC
null
null
C[C@H](N)CNc1ccc(OC(F)(F)F)cc1.O=C(O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1>CN(C)C=O.C(Cl)Cl.C(C)(=O)OCC>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@H](CCC1CCCCC1)CC(=O)N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-363979f881834f339393193845b4e342
C=CC(=O)O.C=CCC(C)(C)C>>CC(C)(C)CC=CC(=O)O
CC(CC=C)(C)C.C(C=C)(=O)O>>CC(CC=CC(=O)O)(C)C
[CH2:6]=[CH:7][C:8](=[O:9])[OH:10].C=C[CH2:5][C:2]([CH3:1])([CH3:3])[CH3:4]>>[CH3:1][C:2]([CH3:3])([CH3:4])[CH2:5][CH:6]=[CH:7][C:8](=[O:9])[OH:10]
C=CC(=O)O.C=CCC(C)(C)C
CC(C)(C)CC=CC(=O)O
null
[Ru]
C(Cl)Cl
C-C Coupling
OtherReaction
117d9a19ce3d25c46858e5d44570547905555fd9d79d47e129edbc20f2e9139d
7cc827c291e2a977a7a91dfb00752230897a77bed46038b3e1551b560ca4b6fc
null
C=C-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5].[CH2;D1;+0:6]=[C:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]>>[C;D1;H3:3]-[C:2](-[C;D1;H3:4])(-[C;D1;H3:5])-[CH2;D2;+0:1]-[CH;D2;+0:6]=[C:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]
99
[{"value": 99.0, "product": "CC(CC=CC(=O)O)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.7, "product": "CC(CC=CC(=O)O)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
5,5-Dimethyl-hex-2-enoic acid was prepared using a modified procedure from Chatterjee, A. K. et al. J. Am. Chem. Soc. 2003, 125(37), 11360-11370. 4,4-Dimethyl-1-pentene (5.0 mL, 34.77 mmol, 1.5 eq.) and acrylic acid (1.54 mL, 22.51 mmol, 1.0 eq.) were added to a solution of ruthenium catalyst ([1,3-bis(2,4,6-trimethylp...
10.6084/m9.figshare.5104873.v1
null
Allyl.Vinyl
null
null
null
null
Other
[Ru].C(Cl)Cl
null
null
C=CC(=O)O.C=CCC(C)(C)C>[Ru].C(Cl)Cl>CC(C)(C)CC=CC(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6c4ebff5f0044ba8a0948b33a77e2c07
CC(C)(C)C=O.CCOP(=O)(CC(=O)OC)OCC>>COC(=O)C=CC(C)(C)C
O.[Li]CCCC.C(C)OP(=O)(OCC)CC(=O)OC.CC(C=O)(C)C>>COC(C=CC(C)(C)C)=O
O=[CH:6][C:7]([CH3:8])([CH3:9])[CH3:10].CCOP(=O)(OCC)[CH2:5][C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]=[CH:6][C:7]([CH3:8])([CH3:9])[CH3:10]
CC(C)(C)C=O.CCOP(=O)(CC(=O)OC)OCC
COC(=O)C=CC(C)(C)C
null
null
C1CCOC1
C-C Coupling
Wittig with Phosphonium
a86984aeb4a9963534e0b081b0ecca18455fda1775f36ce168d1ca4cf966df3e
203dd34a20dceaf1737adbf20e01b43c2424e4e4b1722d942d1a796d895396e6
null
C-C-O-P(=O)(-O-C-C)-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].O=[CH;D2;+0:6]-[C:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[C;D1;H3:10]>>[C;D1;H3:8]-[C:7](-[C;D1;H3:9])(-[C;D1;H3:10])-[CH;D2;+0:6]=[CH;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]
null
[]
-78
CELSIUS
20
MINUTE
Methyl diethylphosphonoacetate (13.35 mL, 73.6 mmol, 1.05 eq.) was dissolved in THF (30 mL) and cooled to −78° C. in an acetone-dry ice bath. n-BuLi (1.6M in hexanes) (45.8 mL, 73.2 mmol, 1.05 eq.) was added slowly over 20 min. Trimethylacetaldehyde (6.0 g, 69.6 mmol, 1.0 eq.), was added to the reaction and allowed to ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Ester
Ester
null
null
null
HO-
C1CCOC1
-78
0.333333
CC(C)(C)C=O.CCOP(=O)(CC(=O)OC)OCC>C1CCOC1>COC(=O)C=CC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2c239dc3820e416cbba4e6bf8b0413c1
COC(=O)C=CC(C)(C)C>>COC(=O)CCC(C)(C)C
COC(C=CC(C)(C)C)=O>>COC(CCC(C)(C)C)=O
[CH3:1][O:2][C:3](=[O:4])[CH:5]=[CH:6][C:7]([CH3:8])([CH3:9])[CH3:10]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][CH2:6][C:7]([CH3:8])([CH3:9])[CH3:10]
COC(=O)C=CC(C)(C)C
COC(=O)CCC(C)(C)C
null
[Pd]
CO.C(C)(=O)OCC
Reduction
Hydrogenation (double to single)
c04c38f95d7b746e5bdb99c368a7a33956c97b95b54c7ad89be2a85526386ec9
9a50abf8d2e4cd9195d7a0cadbe97483a261a81cf70b653cfddd5ecf76d383a6
null
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[CH;D2;+0:5]=[CH;D2;+0:6]-[C:7](=[O;D1;H0:8])-[#8:9]-[C;D1;H3:10]>>[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[CH2;D2;+0:5]-[CH2;D2;+0:6]-[C:7](=[O;D1;H0:8])-[#8:9]-[C;D1;H3:10]
81
[{"value": 81.0, "product": "COC(CCC(C)(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.8, "product": "COC(CCC(C)(C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
4,4-Dimethyl-pent-2-enoic acid methyl ester (8.52 g, 60.0 mmol) was dissolved in MeOH (30 mL) and ethyl acetate (30 mL). Palladium on carbon (10 wt %) (˜50 mg) was added to the reaction and was placed under a H2 balloon (1 atm). The reaction was allowed to stir for 12 hours, flushed with nitrogen and filtered over a pa...
10.6084/m9.figshare.5104873.v1
null
Ester
Ester
null
null
null
null
[Pd].CO.C(C)(=O)OCC
null
12
COC(=O)C=CC(C)(C)C>[Pd].CO.C(C)(=O)OCC>COC(=O)CCC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0d4ea798a4f64207a19b310872483710
COC(=O)CCC(C)(C)C>>CC(C)(C)CCC(=O)O
COC(CCC(C)(C)C)=O.[OH-].[Na+]>>CC(CCC(=O)O)(C)C
C[O:9][C:7]([CH2:6][CH2:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:8]>>[CH3:1][C:2]([CH3:3])([CH3:4])[CH2:5][CH2:6][C:7](=[O:8])[OH:9]
COC(=O)CCC(C)(C)C
CC(C)(C)CCC(=O)O
null
null
O.C(Cl)Cl
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
null
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
85
[{"value": 85.0, "product": "CC(CCC(=O)O)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.7, "product": "CC(CCC(=O)O)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4.5
HOUR
4,4-Dimethyl-pentanoic acid methyl ester (7.0 g, 48.5 mmol, 1.0 eq.) was treated with a solution of NaOH (4.0 g, 100 mmol, 2.1 eq.) in water (5 mL). The homogeneous solution was allowed to stir for 4-5 hours. The reaction was diluted with CH2Cl2 and the aqueous layer was extracted with CH2Cl2 (50 mL×3). The aqueous lay...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
null
Other
O.C(Cl)Cl
null
4.5
COC(=O)CCC(C)(C)C>O.C(Cl)Cl>CC(C)(C)CCC(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7382ee2eb4ff48368b5a9b8708fcd1a2
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCSCC1)CC1CCCCC1>>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCS(=O)(=O)CC1)CC1CCCCC1
OOS(=O)[O-].[K+].C1(CCCCC1)C[C@@H](C(=O)N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)CC(N1CCSCC1)=O>>C1(CCCCC1)C[C@@H](C(=O)N[C@H](CNC1=CC=C(C=C1)OC(F)(F)F)C)CC(=O)N1CCS(CC1)(=O)=O
[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7][c:8]([O:9][C:10]([F:11])([F:12])[F:13])[cH:14][cH:15]1)[NH:16][C:17](=[O:18])[C@@H:19]([CH2:20][C:21](=[O:22])[N:23]1[CH2:24][CH2:25][S:26][CH2:29][CH2:30]1)[CH2:31][CH:32]1[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1>>[CH3:1][C@@H:2]([CH2:3][NH:4][c:5]1[cH:6][cH:7][c:8]([O:...
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCSCC1)CC1CCCCC1
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCS(=O)(=O)CC1)CC1CCCCC1
null
null
null
Oxidation
OtherReaction
4e68790434c882ffa16cbefcd9615ee85d2b208cef00d7ba37514eb822eb67a9
5cedc1bf0f43f21d78a249521ecfcec19fc5ac4895c41eed0e84f0c2618149fa
O=C(NCCNc1ccccc1)[C@@H](CC(=O)N1CCS(=O)(=O)CC1)CC1CCCCC1
[#7:1]1-[C:2]-[C:3]-[S;H0;D2;+0:4]-[C:5]-[C:6]-1>>[O;D1;H0:7]=[S;H0;D4;+0:4]1(=[O;D1;H0:8])-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
null
[]
null
null
null
null
The compound was synthesized in a similar fashion to Example 6. An OXONE oxidation was employed title compound of Example 51 to furnish the sulfone. A procedure was used as described in McCarthy, J. R. et al. Org. Synth., CV9, 446. 1H NMR (CD3OD, 400 MHz) δ 0.73-0.79 (m, 2H), 1.00-1.19 (m, 7H), 1.10 (d, J=6.8 Hz), 1.34...
10.6084/m9.figshare.5104873.v1
null
Monosulfide
Sulfone
C1CSCC[NH]1
C1CSCC[NH]1
c1ccccc1.C1CSCC[NH]1.C1CCCCC1
null
null
null
null
C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCSCC1)CC1CCCCC1>>C[C@@H](CNc1ccc(OC(F)(F)F)cc1)NC(=O)[C@@H](CC(=O)N1CCS(=O)(=O)CC1)CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-982f8fedc2954565b07439f8735834fd
CC(C)[C@H](N)CO.O=C(O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1>>CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
C(C)(C)N(CC)C(C)C.FC1=CC=C(C=C1)[C@@H](C(=O)O)CC(=O)N1CCOCC1.N[C@H](CO)C(C)C.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F>>FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)CO)CC(=O)N1CCOCC1
[CH3:1][CH:2]([CH3:3])[C@@H:4]([CH2:5][OH:6])[NH2:7].O[C:8](=[O:9])[C@@H:10]([CH2:11][C:12](=[O:13])[N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)[c:20]1[cH:21][cH:22][c:23]([F:24])[cH:25][cH:26]1>>[CH3:1][CH:2]([CH3:3])[C@@H:4]([CH2:5][OH:6])[NH:7][C:8](=[O:9])[C@@H:10]([CH2:11][C:12](=[O:13])[N:14]1[CH2:15][CH2:16][...
CC(C)[C@H](N)CO.O=C(O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
null
null
CCCCCC.C(Cl)Cl.CCOC(=O)C
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(CCc1ccccc1)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[c:4])-[C:5]-[C:6](-[#7:7])=[O;D1;H0:8].[C:9]-[C:10](-[C:11])-[NH2;D1;+0:12]>>[#7:7]-[C:6](=[O;D1;H0:8])-[C:5]-[C:3](-[c:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:12]-[C:10](-[C:9])-[C:11]
41
[{"value": 41.0, "product": "FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)CO)CC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 40.6, "product": "FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)CO)CC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid (2.00 g, 7.11 mmol, 1.0 eq.), 2-(S)-Amino-3-methyl-butan-1-ol (1.59 g, 7.33 mmol, 1.03 eq.) and HATU (2.41 g, 7.33 mmol, 1.03 mmol) were dissolved in CH2Cl2 and stirred at room temperature. Diisopropylethylamine (3.9 mL, 21.98 mmol, 3.1 eq.) was added via syri...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
C1COCC[NH]1.c1ccccc1
HO-
CCCCCC.C(Cl)Cl.CCOC(=O)C
null
null
CC(C)[C@H](N)CO.O=C(O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1>CCCCCC.C(Cl)Cl.CCOC(=O)C>CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ed10a5a388014fa48116a42541cc0bf6
CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1>>CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)CO)CC(=O)N1CCOCC1.CC(=O)OI1(C=2C=CC=CC2C(=O)O1)(OC(=O)C)OC(=O)C>>FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)C=O)CC(=O)N1CCOCC1
[CH3:1][CH:2]([CH3:3])[C@@H:4]([CH2:5][OH:6])[NH:7][C:8](=[O:9])[C@@H:10]([CH2:11][C:12](=[O:13])[N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)[c:20]1[cH:21][cH:22][c:23]([F:24])[cH:25][cH:26]1>>[CH3:1][CH:2]([CH3:3])[C@@H:4]([CH:5]=[O:6])[NH:7][C:8](=[O:9])[C@@H:10]([CH2:11][C:12](=[O:13])[N:14]1[CH2:15][CH2:16][O:17...
CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
null
null
C(Cl)Cl.CCOC(=O)C
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
O=C(CCc1ccccc1)N1CCOCC1
[C:1]-[C:2](-[#7:3]-[C:4]=[O;D1;H0:5])-[CH2;D2;+0:6]-[OH;D1;+0:7]>>[C:1]-[C:2](-[#7:3]-[C:4]=[O;D1;H0:5])-[CH;D2;+0:6]=[O;H0;D1;+0:7]
62
[{"value": 62.0, "product": "FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)C=O)CC(=O)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.7, "product": "FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)C=O)CC(=O)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide (2.31 g, 6.30 mmol, 1.0 eq.) was dissolved in CH2Cl2 (32 mL) and stirred at room temperature. Dess-Martin Periodinane (2.67 g, 6.30 mmol, 1.0 eq.) was added in one portion and the reaction is monitored by LC/MS and TLC. Up...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
C1COCC[NH]1.c1ccccc1
null
C(Cl)Cl.CCOC(=O)C
null
null
CC(C)[C@@H](CO)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1>C(Cl)Cl.CCOC(=O)C>CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-950430614803451d89e67ca6730e7c21
CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1.COc1ccc(N)cn1>>COc1ccc(NC[C@@H](NC(=O)[C@@H](CC(=O)N2CCOCC2)c2ccc(F)cc2)C(C)C)cn1
C(#N)[BH3-].[Na+].FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)C=O)CC(=O)N1CCOCC1.NC=1C=CC(=NC1)OC.C(C)(=O)O>>FC1=CC=C(C=C1)[C@@H](C(=O)N[C@@H](C(C)C)CNC=1C=NC(=CC1)OC)CC(=O)N1CCOCC1
O=[CH:8][C@@H:9]([NH:10][C:11](=[O:12])[C@@H:13]([CH2:14][C:15](=[O:16])[N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1)[c:23]1[cH:24][cH:25][c:26]([F:27])[cH:28][cH:29]1)[CH:30]([CH3:31])[CH3:32].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[cH:33][n:34]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([NH:7][CH2:8][C@@H:9]([NH:10...
CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1.COc1ccc(N)cn1
COc1ccc(NC[C@@H](NC(=O)[C@@H](CC(=O)N2CCOCC2)c2ccc(F)cc2)C(C)C)cn1
null
null
CO
Heteroatom Alkylation and Arylation
Reductive amination with aldehyde
422be648aea52bce28ccc8fb32ec3178aaa47bbd624f063874619362f075b5f2
7915721a3e395aed85e3c40dc4d725c571a931ac517c6a0da16f2a2b0bb5eac7
O=C(NCCNc1cccnc1)[C@@H](CC(=O)N1CCOCC1)c1ccccc1
O=[CH;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]:[#7;a:11]:[c:12]>>[C:3]-[C:2](-[#7:4]-[C:5]=[O;D1;H0:6])-[CH2;D2;+0:1]-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]:[#7;a:11]:[c:12]
null
[]
null
null
null
null
2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-formyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide (350 mg, 0.96 mmol, 1.0 eq.) and 5-Amino-2-methoxy-pyridine (240 μL, 1.92 mmol, 2.0 eq.) dissolved in MeOH (2.5 mL) and acetic acid (106 mL, 1.92 mmol, 2.0 eq.) added via syringe at room temperature. Sodium cyanoborohydride (121 ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Secondary amine
null
null
c1ccncc1.C1COCC[NH]1.c1ccccc1
Other
CO
null
null
CC(C)[C@@H](C=O)NC(=O)[C@@H](CC(=O)N1CCOCC1)c1ccc(F)cc1.COc1ccc(N)cn1>CO>COc1ccc(NC[C@@H](NC(=O)[C@@H](CC(=O)N2CCOCC2)c2ccc(F)cc2)C(C)C)cn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bd9245b2f7094d11a58f50b566c68df3
C=C1CCC(C(=O)OCC)CC1>>C=C1CCC(CO)CC1
C(C)OC(=O)C1CCC(CC1)=C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>C=C1CCC(CC1)CO
CCO[C:6]([CH:5]1[CH2:4][CH2:3][C:2](=[CH2:1])[CH2:9][CH2:8]1)=[O:7]>>[CH2:1]=[C:2]1[CH2:3][CH2:4][CH:5]([CH2:6][OH:7])[CH2:8][CH2:9]1
C=C1CCC(C(=O)OCC)CC1
C=C1CCC(CO)CC1
null
null
null
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C=C1CCCCC1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3](-[C:4])-[C:5]>>[C:4]-[C:3](-[CH2;D2;+0:1]-[OH;D1;+0:2])-[C:5]
null
[]
null
null
null
null
The reduction reaction of 4-methylene-cyclohexanecarboxylic acid ethyl ester with LAH is as described in the above reference. The product was purified by distillation to provide (4-methylene-cyclohexyl)-methanol as clear oil (3.67 g, 29.09 mmol, 50% over Step A and B). Conditions: See reaction.notes.procedure_details. ...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1CCCCC1
HO-
null
null
null
C=C1CCC(C(=O)OCC)CC1>>C=C1CCC(CO)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-98383634377349609046a0d1ae6cb608
OCC1CCC2(CC1)CC2>>O=CC1CCC2(CC1)CC2
C1CC12CCC(CC2)CO.[Cr](=O)(=O)([O-])O[Cr](=O)(=O)[O-].[NH+]1=CC=CC=C1.[NH+]1=CC=CC=C1>>C1CC12CCC(CC2)C=O
[OH:1][CH2:2][CH:3]1[CH2:4][CH2:5][C:6]2([CH2:7][CH2:8]1)[CH2:9][CH2:10]2>>[O:1]=[CH:2][CH:3]1[CH2:4][CH2:5][C:6]2([CH2:7][CH2:8]1)[CH2:9][CH2:10]2
OCC1CCC2(CC1)CC2
O=CC1CCC2(CC1)CC2
null
null
C(Cl)Cl
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
C1CCC2(CC1)CC2
[C:1]-[C:2](-[CH2;D2;+0:3]-[OH;D1;+0:4])-[C:5]>>[C:1]-[C:2](-[CH;D2;+0:3]=[O;H0;D1;+0:4])-[C:5]
null
[]
null
null
null
null
Spiro[2.5]oct-6-yl-methanol (2.57 g, 18.3 mmol, 1.0 eq.) was dissolved in CH2Cl2 (30 mL) and placed in a ice-water bath at 0° C. Pyridinium dichromate (PCC) (7.9 g, 36.6 mmol, 2.0 eq.) was added and the reaction warmed to room temperature for 4 hours with stirring. The crude reaction was filtered through a Celite pad a...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
C1CCC2(CC1)CC2
null
C(Cl)Cl
null
null
OCC1CCC2(CC1)CC2>C(Cl)Cl>O=CC1CCC2(CC1)CC2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-da02151b449d42cbbe103aa172662fa2
COC(=O)[C@@H](O)CSCc1ccccc1>>O=C(O)[C@@H](O)CSCc1ccccc1
COC([C@H](CSCC1=CC=CC=C1)O)=O.[OH-].[Li+]>>C(C1=CC=CC=C1)SC[C@@H](C(=O)O)O
C[O:3][C:2](=[O:1])[C@@H:4]([OH:5])[CH2:6][S:7][CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[O:1]=[C:2]([OH:3])[C@@H:4]([OH:5])[CH2:6][S:7][CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1
COC(=O)[C@@H](O)CSCc1ccccc1
O=C(O)[C@@H](O)CSCc1ccccc1
null
null
null
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccccc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
46
[{"value": 46.0, "product": "C(C1=CC=CC=C1)SC[C@@H](C(=O)O)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This reaction was performed as previously described by Deechongkit, S.; You, S.-L.; Kelly, J. W. Org. Lett. 2004, 6, 497, using (R)-3-Benzylsulfanyl-2-hydroxy-propionic acid methyl ester 110b and lithium hydroxide. (R)-3-Benzylsulfanyl-2-hydroxy-propionic acid 110c (3.08 g, 14.51 mmol, 46%) was isolated as a viscous oi...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1
Other
null
null
null
COC(=O)[C@@H](O)CSCc1ccccc1>>O=C(O)[C@@H](O)CSCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7d4f59b686e344d1bf374226933acbae
CCOC(C)=O.COc1ccc2c(c1)CCC(c1ccccc1)=C2C(O)c1ccc(OCCN2CCCC2)cc1>>COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2CC1)OC)C(O)C1=CC=C(C=C1)OCCN1CCCC1.C(C)(=O)OCC.Cl.C(C)(=O)OCC>>Cl.C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)OC)CC1=CC=C(C=C1)OCCN1CCCCC1
CC(=O)OC[CH3:19].O[CH:8]([C:7]1=[C:24]([c:25]2[cH:26][cH:27][cH:28][cH:29][cH:30]2)[CH2:31][CH2:32][c:33]2[c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:34]2)[c:9]1[cH:10][cH:11][c:12]([O:13][CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][CH2:20][CH2:21]2)[cH:22][cH:23]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([CH2:8][c:9]3[cH:10...
CCOC(C)=O.COc1ccc2c(c1)CCC(c1ccccc1)=C2C(O)c1ccc(OCCN2CCCC2)cc1
COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
null
null
null
C-C Coupling
OtherReaction
2957d45d0c4fb28629395caf7bb4bede51ca9d5a4978360cfacccd6f227c82b4
85dc278ba9c307395886aa35ef1fcafb5013915b72e73ef6ca23953dd492bbfb
c1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCCC3)cc2)cc1
C-C(=O)-O-C-[CH3;D1;+0:1].O-[CH;D3;+0:2](-[C;H0;D3;+0:3]1=[C;H0;D3;+0:4](-[c;H0;D3;+0:5](:[c:6]:[c:7]):[c:8]:[c:9])-[CH2;D2;+0:10]-[CH2;D2;+0:11]-[c:12](:[c:13]):[c:14]-1:[c:15])-[c:16](:[c:17]):[c:18].[C:19]-[#7:20]1-[C:21]-[CH2;D2;+0:22]-[CH2;D2;+0:23]-[C:24]-1>>[C:19]-[#7:20]1-[C:21]-[CH2;D2;+0:22]-[CH2;D2;+0:1]-[CH...
89
[{"value": 89.0, "product": "Cl.C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)OC)CC1=CC=C(C=C1)OCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
0.5
MINUTE
To a solution of the product of Example 7 (8.7 g, 18.5 mmol) stirring in ethyl acetate (100 mL) was added a saturated solution of hydrochloric acid gas in ethyl acetate (250 mL). After 0.5 min, the resulting solution was concentrated to give 8.0 g (89%) of the desired product as a white foam which was used without furt...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary alcohol
null
C1=Cc2ccccc2CC1.C1CC[NH]C1
C1CC[NH]CC1.c1ccc2ccccc2c1
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccc2ccccc2c1
HO-
null
null
0.008333
CCOC(C)=O.COc1ccc2c(c1)CCC(c1ccccc1)=C2C(O)c1ccc(OCCN2CCCC2)cc1>>COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e8449c6acb0f4a579849e68b76896835
COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1>>Oc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
Cl.C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)OC)CC1=CC=C(C=C1)OCCN1CCCCC1.B(Cl)(Cl)Cl.CO>>C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)O)CC1=CC=C(C=C1)OCCN1CCCCC1
C[O:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([CH2:7][c:8]3[cH:9][cH:10][c:11]([O:12][CH2:13][CH2:14][N:15]4[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]4)[cH:21][cH:22]3)[c:23](-[c:24]3[cH:25][cH:26][cH:27][cH:28][cH:29]3)[cH:30][cH:31][c:32]2[cH:33]1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([CH2:7][c:8]3[cH:9][cH:10][c:11]([O:12][CH2:1...
COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
Oc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
null
null
ClCCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCCC3)cc2)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
77.1
[{"value": 63.0, "product": "C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)O)CC1=CC=C(C=C1)OCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.1, "product": "C1(=CC=CC=C1)C1=C(C2=CC=C(C=C2C=C1)O)CC1=CC=C(C=C1)OCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of the product of Example 9 (4.0 g, 8.0 mmol) stirring in 1,2-dichloroethane (50 mL) at 0° C. was added boron trichloride (10 mL, 117.0 mmol). The resulting dark purple solution was stirred at room temperature overnight in a sealed tube then cooled to 0° C. Methanol (50 mL) was carefully added dropwise ov...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccc2ccccc2c1
Other
ClCCCl
null
8
COc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1>ClCCCl>Oc1ccc2c(Cc3ccc(OCCN4CCCCC4)cc3)c(-c3ccccc3)ccc2c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ad44e7ac7b774522b622396f93e5e114
COc1ccc(C2=C(C(O)c3ccc(OCCN4CCCC4)cc3)c3ccccc3CC2)cc1>>COc1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
COC1=CC=C(C=C1)C1=C(C2=CC=CC=C2CC1)C(O)C1=CC=C(C=C1)OCCN1CCCC1.Cl>>Cl.COC1=CC=C(C=C1)C1=C(C2=CC=CC=C2C=C1)CC1=CC=C(C=C1)OCCN1CCCC1
O[CH:17]([C:16]1=[C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:33][cH:32]2)[CH2:8][CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]21)[c:18]1[cH:19][cH:20][c:21]([O:22][CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)[cH:30][cH:31]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][cH:9][c:10]3[cH:11][cH:12][c...
COc1ccc(C2=C(C(O)c3ccc(OCCN4CCCC4)cc3)c3ccccc3CC2)cc1
COc1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
null
null
CO
Reduction
OtherReaction
993798e8877653e2916ebad5ce02cd2f327385a2c7261328e2a315c7a52a0875
46f8a11b80b06e754a5a34198d843342612a5e7ede950bda52ce3a500cedba0b
c1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
O-[CH;D3;+0:1](-[C;H0;D3;+0:2]1=[C;H0;D3;+0:3](-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8])-[CH2;D2;+0:9]-[CH2;D2;+0:10]-[c:11](:[c:12]):[c:13]-1:[c:14])-[c:15](:[c:16]):[c:17]>>[c:12]:[c:11]1:[cH;D2;+0:10]:[cH;D2;+0:9]:[c;H0;D3;+0:3](-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8]):[c;H0;D3;+0:2](-[CH2;D2;+0:1]-[c:15](:[c:16]...
null
[]
-20
CELSIUS
null
null
To a solution of the product of Example 14 (2.0 g, 4.58 mmol) stirring in methanol (50 mL) at ambient temperature was added methanolic hydrochloric acid (10 mL of a saturated solution). The reaction mixture was then concentrated to 20 mL and cooled to −20° C. for several hours. Filtration gave 0.62 g of the desired pro...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
null
C1=Cc2ccccc2CC1
c1ccc2ccccc2c1
c1ccccc1.c1ccc2ccccc2c1.c1ccccc1.C1CC[NH]C1
HO-
CO
-20
null
COc1ccc(C2=C(C(O)c3ccc(OCCN4CCCC4)cc3)c3ccccc3CC2)cc1>CO>COc1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9b1d83f0de6c4b3fabb8088122a431b3
COc1ccc(-c2ccc3cc(OC)ccc3c2-c2cc(OCCN3CCCC3)ccc2C)cc1>>Cc1ccc(OCCN2CCCC2)cc1-c1c(-c2ccc(O)cc2)ccc2cc(O)ccc12
Cl.COC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)OC)C1=C(C=CC(=C1)OCCN1CCCC1)C.B(Cl)(Cl)Cl.CO>>OC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)O)C1=C(C=CC(=C1)OCCN1CCCC1)C
C[O:22][c:21]1[cH:20][cH:19][c:18](-[c:17]2[c:16](-[c:15]3[c:2]([CH3:1])[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][N:9]4[CH2:10][CH2:11][CH2:12][CH2:13]4)[cH:14]3)[c:33]3[c:27]([cH:26][cH:25]2)[cH:28][c:29]([O:30]C)[cH:31][cH:32]3)[cH:24][cH:23]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:10][CH2:11][CH2:...
COc1ccc(-c2ccc3cc(OC)ccc3c2-c2cc(OCCN3CCCC3)ccc2C)cc1
Cc1ccc(OCCN2CCCC2)cc1-c1c(-c2ccc(O)cc2)ccc2cc(O)ccc12
null
null
ClCCCl
Deprotection
OtherReaction
a0f05885bbc65ae2846cad0ac34029941211b2ef3a426958b0c8aa83bb16fe86
9df751cd682ad9d54ed75d7313aaead6a019c5d37ede15c4672866d319b900ff
c1ccc(-c2ccc3ccccc3c2-c2cccc(OCCN3CCCC3)c2)cc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4].C-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]
29.8
[{"value": 27.0, "product": "OC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)O)C1=C(C=CC(=C1)OCCN1CCCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.8, "product": "OC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)O)C1=C(C=CC(=C1)OCCN1CCCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of the product of Example 18 (1.61 g, 2.60 mmol) in 1.2-dichloroethane (30 mL) stirring at 0° C. was added boron trichloride (10 ml, 117 mmol). The resulting dark purple solution was stirred overnight at ambient temperature in a sealed tube. After cooling the solution to 0° C., methanol (25 mL) was carefu...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Aromatic alcohol.Aromatic alcohol
null
null
c1ccccc1.C1CC[NH]C1.c1ccccc1.c1ccc2ccccc2c1
Other
ClCCCl
null
8
COc1ccc(-c2ccc3cc(OC)ccc3c2-c2cc(OCCN3CCCC3)ccc2C)cc1>ClCCCl>Cc1ccc(OCCN2CCCC2)cc1-c1c(-c2ccc(O)cc2)ccc2cc(O)ccc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dc057ad441ce406a8baaa2d771d26321
COc1ccc(C2=C(C(O)c3ccc(OCCCN4CCCCC4)cc3)c3ccc(OC)cc3CC2)cc1>>COc1ccc(-c2ccc3cc(OC)ccc3c2Cc2ccc(OCCCN3CCCCC3)cc2)cc1
COC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2CC1)OC)C(O)C1=CC=C(C=C1)OCCCN1CCCCC1.Cl>>Cl.COC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)OC)CC1=CC=C(C=C1)OCCCN1CCCCC1
O[CH:19]([C:18]1=[C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:37][cH:36]2)[CH2:8][CH2:9][c:10]2[cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16][c:17]21)[c:20]1[cH:21][cH:22][c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]2)[cH:34][cH:35]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:...
COc1ccc(C2=C(C(O)c3ccc(OCCCN4CCCCC4)cc3)c3ccc(OC)cc3CC2)cc1
COc1ccc(-c2ccc3cc(OC)ccc3c2Cc2ccc(OCCCN3CCCCC3)cc2)cc1
null
null
C(C)(=O)OCC
Reduction
OtherReaction
993798e8877653e2916ebad5ce02cd2f327385a2c7261328e2a315c7a52a0875
46f8a11b80b06e754a5a34198d843342612a5e7ede950bda52ce3a500cedba0b
c1ccc(-c2ccc3ccccc3c2Cc2ccc(OCCCN3CCCCC3)cc2)cc1
O-[CH;D3;+0:1](-[C;H0;D3;+0:2]1=[C;H0;D3;+0:3](-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8])-[CH2;D2;+0:9]-[CH2;D2;+0:10]-[c:11](:[c:12]):[c:13]-1:[c:14])-[c:15](:[c:16]):[c:17]>>[c:12]:[c:11]1:[cH;D2;+0:10]:[cH;D2;+0:9]:[c;H0;D3;+0:3](-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8]):[c;H0;D3;+0:2](-[CH2;D2;+0:1]-[c:15](:[c:16]...
97
[{"value": 97.0, "product": "Cl.COC1=CC=C(C=C1)C1=C(C2=CC=C(C=C2C=C1)OC)CC1=CC=C(C=C1)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Reaction of the product of Example 21 (1.5 g, 2.9 mmol) with hydrochloric acid (50 mL of a saturated ethyl acetate solution) in ethyl acetate (50 mL) according to the procedure in Example 18 gave a 97% yield of the desired product: 1H-NMR (300 MHz, CDCl3) δ 7.70-7.80 (m, 2H), 7.42 (d, J=8.4 Hz, 1H), 7.15-7.30 (m, 3H), ...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
null
C1=Cc2ccccc2CC1
c1ccc2ccccc2c1
c1ccccc1.c1ccc2ccccc2c1.c1ccccc1.C1CC[NH]CC1
HO-
C(C)(=O)OCC
null
null
COc1ccc(C2=C(C(O)c3ccc(OCCCN4CCCCC4)cc3)c3ccc(OC)cc3CC2)cc1>C(C)(=O)OCC>COc1ccc(-c2ccc3cc(OC)ccc3c2Cc2ccc(OCCCN3CCCCC3)cc2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9ef2e52800084124aa06cb2024b3092f
CC(=O)c1ccccn1.COC(=O)C(=O)[O-]>>COC(=O)C(O)=CC(=O)c1cccnc1
Cl.C(C)(=O)C1=NC=CC=C1.C(C(=O)[O-])(=O)OC.CO.C[O-].[Na+]>>COC(C(=CC(C=1C=NC=CC1)=O)O)=O
[CH3:7][C:8](=[O:9])[c:10]1[cH:11][cH:12][cH:13][cH:15][n:14]1.[O-][C:5]([C:3]([O:2][CH3:1])=[O:4])=[O:6]>>[CH3:1][O:2][C:3](=[O:4])[C:5]([OH:6])=[CH:7][C:8](=[O:9])[c:10]1[cH:11][cH:12][cH:13][n:14][cH:15]1
CC(=O)c1ccccn1.COC(=O)C(=O)[O-]
COC(=O)C(O)=CC(=O)c1cccnc1
null
null
null
C-C Coupling
OtherReaction
41ecb874d1a6123b790c013cc0681b994f2c9ce6c828e5f6f24a6cd098ee46cf
4c8da19c226c76fb5f286d8c34536e387adc6ed030260abb13908c23f0221ea1
c1ccncc1
[C;D1;H3:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[C;H0;D3;+0:5](-[O-])=[O;H0;D1;+0:6].[CH3;D1;+0:7]-[C:8](=[O;D1;H0:9])-[c;H0;D3;+0:10]1:[c:11]:[c:12]:[cH;D2;+0:13]:[cH;D2;+0:14]:[n;H0;D2;+0:15]:1>>[C;D1;H3:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[C;H0;D3;+0:5](-[OH;D1;+0:6])=[CH;D2;+0:7]-[C:8](=[O;D1;H0:9])-[c;H0;D3;+0:10]1:[c:11]:[c:12]...
null
[]
null
null
15
MINUTE
Acetyl pyridine (1.81 mL, 16.5 mmol) and methyl oxalate (3.12 g, 26.4 mmol) were dissolved in MeOH (30 mL, anhydrous). Sodium methoxide (6.9 mL, 25% in MeOH) was added over 10 min. Reaction solidified and was complete after 15 minutes. The solid mass was dissolved when acidified with HCl (10%, aqueous). The pH was then...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester
Ketone.Ester.Enol
c1ccncc1
c1ccncc1
c1ccncc1
HO-
null
null
0.25
CC(=O)c1ccccn1.COC(=O)C(=O)[O-]>>COC(=O)C(O)=CC(=O)c1cccnc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f5aed28b2a534cc69f7da8f20e43ea6a
COC(=O)C(O)=CC(=O)c1cccnc1.NNc1ccc(Cl)c(Cl)c1>>COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
COC(C(=CC(C=1C=NC=CC1)=O)O)=O.Cl.ClC=1C=C(C=CC1Cl)NN>>Cl.COC(=O)C1=NN(C(=C1)C=1C=NC=CC1)C1=CC(=C(C=C1)Cl)Cl
O=[C:7]([CH:6]=[C:5](O)[C:3]([O:2][CH3:1])=[O:4])[c:8]1[cH:9][cH:10][cH:11][n:12][cH:13]1.[NH:14]([c:15]1[cH:16][cH:17][c:18]([Cl:19])[c:20]([Cl:21])[cH:22]1)[NH2:23]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7](-[c:8]2[cH:9][cH:10][cH:11][n:12][cH:13]2)[n:14](-[c:15]2[cH:16][cH:17][c:18]([Cl:19])[c:20]([Cl:21])[cH:22]2...
COC(=O)C(O)=CC(=O)c1cccnc1.NNc1ccc(Cl)c(Cl)c1
COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
null
null
CCO
Aromatic Heterocycle Formation
OtherReaction
33fc2e04255bbdd64fba97753a6f26842e3fecdd69cce27401cb60480f0a7288
bd726ca0015f6098456e848ff1ee644dfe9256f0c8347a12b063c9b5b821ebd7
c1ccc(-n2nccc2-c2cccnc2)cc1
O-[C;H0;D3;+0:1](=[CH;D2;+0:2]-[C;H0;D3;+0:3](=O)-[c;H0;D3;+0:4]1:[c:5]:[#7;a:6]:[c:7]:[c:8]:[c:9]:1)-[C:10](=[O;D1;H0:11])-[#8:12]-[C;D1;H3:13].[NH2;D1;+0:14]-[NH;D2;+0:15]-[c;H0;D3;+0:16](:[c:17]:[c:18]):[c:19]:[c:20]>>[C;D1;H3:13]-[#8:12]-[C:10](=[O;D1;H0:11])-[c;H0;D3;+0:1]1:[cH;D2;+0:2]:[c;H0;D3;+0:3](-[c;H0;D3;+0...
128
[{"value": 70.0, "product": "Cl.COC(=O)C1=NN(C(=C1)C=1C=NC=CC1)C1=CC(=C(C=C1)Cl)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 128.0, "product": "Cl.COC(=O)C1=NN(C(=C1)C=1C=NC=CC1)C1=CC(=C(C=C1)Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
To a solution of 1 (2.90 g, 14.0 mmol) in EtOH (60 mL, anhydrous) was added 3,4-dichlorophenyl hydrazine hydrochloride (3.29 g, 15.4 mmol). The solution was heated to reflux for 30 min and then cooled to 0° C. The precipitate was collected by filtration and washed with H2O and MeOH to yield 2 (3.79 g, 70%) as an off-wh...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Ester.Enol
Ester
null
c1cc[nH]n1
c1cc[nH]n1.c1ccncc1.c1ccccc1
HO-
CCO
0
null
COC(=O)C(O)=CC(=O)c1cccnc1.NNc1ccc(Cl)c(Cl)c1>CCO>COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2b78ff2d3f9b42b2824d22f2c0de4457
COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>[N-]=[N+]=NC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
C(C)N(CC)CC.Cl.COC(=O)C1=NN(C(=C1)C=1C=NC=CC1)C1=CC(=C(C=C1)Cl)Cl.C(C)(C)(C)O.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-]>>ClC=1C=C(C=CC1Cl)N1N=C(C=C1C=1C=NC=CC1)C(=O)N=[N+]=[N-]
CO[C:4](=[O:5])[c:6]1[cH:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][n:13][cH:14]2)[n:15](-[c:16]2[cH:17][cH:18][c:19]([Cl:20])[c:21]([Cl:22])[cH:23]2)[n:24]1.O=P(c1ccccc1)(c1ccccc1)[N:3]=[N+:2]=[N-:1]>>[N-:1]=[N+:2]=[N:3][C:4](=[O:5])[c:6]1[cH:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][n:13][cH:14]2)[n:15](-[c:16]2[cH:17][cH:18][c...
COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
[N-]=[N+]=NC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
null
null
CN(C)C=O
Acylation
OtherReaction
7a7fbf95c42bedc701751c2ac46610ef4946f6e1aaab767c9db970462abf9de2
da67ad6d8377f1cd9033aeb7148ee43a2ffc587f4fbff78d156d7a1ce69356d7
c1ccc(-n2nccc2-c2cccnc2)cc1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[#7;a:4]:[#7;a:5](-[c:6]):[c:7]:[c:8]:1.O=P(-[N;H0;D2;+0:9]=[#7;+:10]=[N;-;D1;H0:11])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[N;-;D1;H0:11]=[#7;+:10]=[N;H0;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[#7;a:4]:[#7;a:5](-[c:6]):[c:7]:[c:8]:1
null
[]
0
CELSIUS
1
HOUR
A solution of 3 (100 mg, 0.27 mmol) and t-butyl alcohol (28.4 μL, 0.30 mmol) in DMF (5 mL, anhydrous) was cooled to 0° C. Diphenylphosphoryl azide (64 μL, 0.30 mmol) was added to the solution. Triethylamine (103 μL, 0.60 mmol) was then added over 10 min. The solution was stirred 1 h at 0° C. and allowed to warm to room...
10.6084/m9.figshare.5104873.v1
null
Ester.Azide
Azide
c1ccccc1.c1ccccc1
null
c1cc[nH]n1.c1ccncc1.c1ccccc1
HO-
CN(C)C=O
0
1
COC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>CN(C)C=O>[N-]=[N+]=NC(=O)c1cc(-c2cccnc2)n(-c2ccc(Cl)c(Cl)c2)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a14940a24cf345248637d1b5745da86a
COC(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1>>COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
ClC(=O)OC.FC1=C(C=C(N)C=C1)[N+](=O)[O-].CCN(C(C)C)C(C)C>>COC(NC1=CC(=C(C=C1)F)[N+](=O)[O-])=O
Cl[C:3]([O:2][CH3:1])=[O:4].[NH2:5][c:6]1[cH:7][cH:8][c:9]([F:10])[c:11]([N+:12](=[O:13])[O-:14])[cH:15]1>>[CH3:1][O:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([F:10])[c:11]([N+:12](=[O:13])[O-:14])[cH:15]1
COC(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1
COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
null
null
ClCCl
Protection
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
038720aa61a7efa0f2a9ee6f2e0adf63a9ffdc2be4697c11a6215baef34f97b2
205f353513ce9506ab61831799da8fb73ec2ef5cfa927664496d3ce72c438860
c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]
null
[]
null
null
8
HOUR
Methyl chloroformate (13.2 mL, 170.2 mmol) was added dropwise to a cold (0° C.) dichloromethane (200 mL) solution of 4-fluoro-3-nitro aniline (24.15 g, 154.7 mmol) and DIPEA (35 mL, 201 mmol). The reaction mixture was stirred at rt overnight. The solution was then diluted with 200 mL of dichloromethane and washed with ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Primary amine
Carbamic ester
null
null
c1ccccc1
HCl
ClCCl
null
8
COC(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1>ClCCl>COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b7cdc726aa8545ffacfb760efffc8f3b
COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>>COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
COC(NC1=CC(=C(C=C1)F)[N+](=O)[O-])=O.C1(CCCCC1)CN>>COC(NC1=CC(=C(C=C1)NCC1CCCCC1)[N+](=O)[O-])=O
F[c:9]1[cH:8][cH:7][c:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[cH:22][c:18]1[N+:19](=[O:20])[O-:21].[NH2:10][CH2:11][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1>>[CH3:1][O:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([NH:10][CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[c:18]([N+:19](=[O:20])[O-:21])[cH:22]...
COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1
COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
null
null
CCO
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NCC2CCCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[C:7]-[C:8]-[NH2;D1;+0:9]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[NH;D2;+0:9]-[C:8]-[C:7]):[c:2]:[c:3]
null
[]
null
null
null
null
Methyl(4-fluoro-3-nitrophenyl)carbamate (1.00 g, 4.67 mmol) and cyclohexylmethyl amine (0.730 mL, 5.60 mmol) were stirred in EtOH (20 mL) containing TEA (1.0 mL, 7.00 mmol) at 75° C. for 24 h. The solvent was concentrated. The residue was dissolved in EtOAc and washed with 5% KHSO4 aqueous solution, saturated NaHCO3 aq...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CCCCC1
HF
CCO
null
null
COC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>CCO>COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e6bcad80cf7741f689703833b32c99fb
COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1>>COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
C1(CCCCC1)CNC1=C(C=C(C=C1)NC(OC)=O)[N+](=O)[O-]>>NC=1C=C(C=CC1NCC1CCCCC1)NC(OC)=O
O=[N+:19]([O-])[c:18]1[c:9]([NH:10][CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[cH:8][cH:7][c:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[cH:20]1>>[CH3:1][O:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([NH:10][CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[c:18]([NH2:19])[cH:20]1
COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
null
null
[Pd].CCOC(=O)C
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(NCC2CCCCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
8
HOUR
Methyl {4-[(cyclohexylmethyl)amino]-3-nitrophenyl}carbamate (1.05 g, 3.42 mmol) was dissolved in 30 mL of EtOAc containing a catalytic amount of 10% Pd/C. The solution was shaken in a Parr hydrogenation apparatus under H2 atmosphere (40 psi) at RT overnight The solution was filtered through Celite and the solvent was e...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.C1CCCCC1
Other
[Pd].CCOC(=O)C
null
8
COC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1>[Pd].CCOC(=O)C>COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a8d54946ad3147e7b2825390666925f5
CC(C)(C)C(=O)Cl.COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1>>COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
NC=1C=C(C=CC1NCC1CCCCC1)NC(OC)=O.CC(C(=O)Cl)(C)C>>COC(NC1=CC2=C(N(C(=N2)C(C)(C)C)CC2CCCCC2)C=C1)=O
O=[C:13](Cl)[C:14]([CH3:15])([CH3:16])[CH3:17].[CH3:1][O:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([NH:18][CH2:19][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[c:10]([NH2:12])[cH:11]1>>[CH3:1][O:2][C:3](=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]2[c:10]([cH:11]1)[n:12][c:13]([C:14]([CH3:15])([CH3:16])[CH3:17])[n:18]2[...
CC(C)(C)C(=O)Cl.COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
null
CN(C)C=1C=CN=CC1
ClCCl
Aromatic Heterocycle Formation
OtherReaction
b48b9f848f2f637750a62e12d0a60718d527408df46b4fc5f95f8aac64874f8d
56ef83dfadec35a1cf1db968b807e178cc4924ce15bf36d774883783cef0f450
c1ccc2c(c1)ncn2CC1CCCCC1
Cl-[C;H0;D3;+0:1](=O)-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5].[C:6]-[C:7]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11](-[NH2;D1;+0:12]):[c:13]>>[C:6]-[C:7]-[n;H0;D3;+0:8]1:[c:9](:[c:10]):[c:11](:[c:13]):[n;H0;D2;+0:12]:[c;H0;D3;+0:1]:1-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5]
null
[]
null
null
1
HOUR
Methyl {3-amino-4-[(cyclohexylmethyl)amino]phenyl}carbamate (950 mg, 3.43 mmol) and DMAP (100 mg, 0.858 mmol) were dissolved in 25 mL of dichloromethane. Trimethylacetyl chloride (0.460 mL, 3.77 mmol) was added dropwise and the solution stirred at RT for 1 h. The solvent was concentrated. The residue was divided in two...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine.Secondary amine
null
c1ccccc1
c1ccc2nc[nH]c2c1
c1ccc2nc[nH]c2c1.C1CCCCC1
HCl
CN(C)C=1C=CN=CC1.ClCCl
null
1
CC(C)(C)C(=O)Cl.COC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1>CN(C)C=1C=CN=CC1.ClCCl>COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d46b3c62044847c4bcb3f8670203ab74
COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1>>CNc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
COC(NC1=CC2=C(N(C(=N2)C(C)(C)C)CC2CCCCC2)C=C1)=O.Cl.CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>C(C)(C)(C)C1=NC2=C(N1CC1CCCCC1)C=CC(=C2)NC
CO[C:1](=O)[NH:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[n:9][c:10]([C:11]([CH3:12])([CH3:13])[CH3:14])[n:15]2[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1>>[CH3:1][NH:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[n:9][c:10]([C:11]([CH3:12])([CH3:13])[CH3:14])[n:15]2[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21...
COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
CNc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
null
null
C1CCOC1
Reduction
OtherReaction
0162385dd3f2239a186ebaf1047930f21ea49a4113c06354aed30cdbf1cd719c
f6bec327410058c9cba187636b48ed5ef90429f24bf839d7fb4e0588ab9ff83e
c1ccc2c(c1)ncn2CC1CCCCC1
C-O-[C;H0;D3;+0:1](=O)-[#7:2]-[c:3]>>[CH3;D1;+0:1]-[#7:2]-[c:3]
null
[]
0
CELSIUS
15
MINUTE
Methyl[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]carbamate (650 mg, 1.89 mmol) was dissolved in 20 mL of THF at 0° C. under nitrogen. 1M HCl/ether (2.65 mL, 2.65 mmol) was added dropwise and the solution stirred at 0° C. for 15 min. LiAlH4 (360 mg, 9.45 mmol) was then slowly added and the solution stirred ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
null
null
null
c1ccc2nc[nH]c2c1.C1CCCCC1
Other
C1CCOC1
0
0.25
COC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1>C1CCOC1>CNc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e930e5e86d4642739fcf31be87fc626e
CC(=O)OC(C)=O.Nc1ccc(F)c([N+](=O)[O-])c1>>CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
FC1=C(C=C(N)C=C1)[N+](=O)[O-].C(C)(=O)OC(C)=O>>FC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-]
CC(=O)O[C:2]([CH3:1])=[O:3].[NH2:4][c:5]1[cH:6][cH:7][c:8]([F:9])[c:10]([N+:11](=[O:12])[O-:13])[cH:14]1>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][cH:7][c:8]([F:9])[c:10]([N+:11](=[O:12])[O-:13])[cH:14]1
CC(=O)OC(C)=O.Nc1ccc(F)c([N+](=O)[O-])c1
CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
null
null
null
Acylation
Aminolysis of esters
87d35e51b477fc9a658a6f307eb56d84c8879182772c9dd3a42ec0d584fd2684
627cbc0550c9f51ad0105d9fcf46677e8c93bed87ee95bfe69292a82550c95b7
c1ccccc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[NH2;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[NH;D2;+0:4]-[c:5](:[c:6]):[c:7]
70
[{"value": 70.0, "product": "FC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
4-Fluoro-3-nitro-aniline (45.0 g, 288.2 mmol) was added portionwise to acetic anhydride (150 mL) at room temperature. The reaction mixture was stirred at room temperature for 2 h. The white solid was collected and dried in vacuo to give the desired title compound (42.0 g, 70%). Conditions: See reaction.notes.procedure_...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Secondary amide
null
null
c1ccccc1
HO-
null
null
2
CC(=O)OC(C)=O.Nc1ccc(F)c([N+](=O)[O-])c1>>CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-34443b7ffb7e4235aaf40ecc280e5e45
CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>>CC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
C1(CCCCC1)CN.FC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-].C([O-])([O-])=O.[Na+].[Na+]>>C1(CCCCC1)CNC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-]
F[c:8]1[cH:7][cH:6][c:5]([NH:4][C:2]([CH3:1])=[O:3])[cH:21][c:17]1[N+:18](=[O:19])[O-:20].[NH2:9][CH2:10][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][cH:7][c:8]([NH:9][CH2:10][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)[c:17]([N+:18](=[O:19])[O-:20])[cH:21]1
CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1
CC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
null
null
O.CCO
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NCC2CCCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[C:7]-[C:8]-[NH2;D1;+0:9]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[NH;D2;+0:9]-[C:8]-[C:7]):[c:2]:[c:3]
113.3
[{"value": 100.0, "product": "C1(CCCCC1)CNC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 113.3, "product": "C1(CCCCC1)CNC1=C(C=C(C=C1)NC(C)=O)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
Cyclohexylmethylamine (2.86 mL, 2.49 g, 22.0 mmol) was added to a mixture of N-(4-fluoro-3-nitrophenyl)acetamide (3.96 g, 20.0 mmol) and sodium carbonate (4.66 g, 44 mmol) in EtOH (50 mL) at room temperature. The reaction mixture was heated for 48 h at 60° C., and diluted with H2O (800 mL). The orange solid was precipi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CCCCC1
HF
O.CCO
60
null
CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>O.CCO>CC(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b6c975447a644a87a3fb29bfe2e09877
CCC(C)(C)c1nc2cc(NC(C)=O)ccc2n1CC1CCCCC1>>CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1
C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)NC(C)=O)C(CC)(C)C.Cl>>C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)N)C(CC)(C)C
CC(=O)[NH:11][c:10]1[cH:9][c:8]2[n:7][c:6]([C:3]([CH2:2][CH3:1])([CH3:4])[CH3:5])[n:15]([CH2:16][CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[c:14]2[cH:13][cH:12]1>>[CH3:1][CH2:2][C:3]([CH3:4])([CH3:5])[c:6]1[n:7][c:8]2[cH:9][c:10]([NH2:11])[cH:12][cH:13][c:14]2[n:15]1[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:2...
CCC(C)(C)c1nc2cc(NC(C)=O)ccc2n1CC1CCCCC1
CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1
null
null
C(C)O
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
c1ccc2c(c1)ncn2CC1CCCCC1
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
127.3
[{"value": 100.0, "product": "C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)N)C(CC)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 127.3, "product": "C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)N)C(CC)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
N-[1-(Cyclohexylmethyl)-2-(1,1-dimethylpropyl)-1H-benzimidazol-5-yl]acetamide (105.4 mg, 0.309 mmol) was dissolved in ethanol (3 mL) and 2N HCl aqueous solution (2 mL) in a Teflon-capped test tube. The vessel was irradiated by microwave for 45 min. at 120° C. After evaporation and drying in vacuo, 117.8 mg (100%) of th...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccc2nc[nH]c2c1.C1CCCCC1
HO-
C(C)O
null
null
CCC(C)(C)c1nc2cc(NC(C)=O)ccc2n1CC1CCCCC1>C(C)O>CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-aba0c9350b3d445eba5866611aea8a27
CCC(C)(C)C(=O)Cl.CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1>>CCC(C)(C)C(=O)Nc1ccc2c(c1)nc(C(C)(C)CC)n2CC1CCCCC1
CC(C(=O)Cl)(CC)C.Cl.C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)N)C(CC)(C)C>>C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)NC(C(CC)(C)C)=O)C(CC)(C)C
Cl[C:6]([C:3]([CH2:2][CH3:1])([CH3:4])[CH3:5])=[O:7].[NH2:8][c:9]1[cH:10][cH:11][c:12]2[c:13]([cH:14]1)[n:15][c:16]([C:17]([CH3:18])([CH3:19])[CH2:20][CH3:21])[n:22]2[CH2:23][CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1>>[CH3:1][CH2:2][C:3]([CH3:4])([CH3:5])[C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][c:12]2[c:13]([cH:1...
CCC(C)(C)C(=O)Cl.CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1
CCC(C)(C)C(=O)Nc1ccc2c(c1)nc(C(C)(C)CC)n2CC1CCCCC1
null
CN(C)C=1C=CN=CC1
C(C)#N.CCOC(=O)C
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
c1ccc2c(c1)ncn2CC1CCCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])(-[C;D1;H3:5])-[C;D1;H3:6].[#7;a:7]:[c:8]:[c:9]:[c:10](-[NH2;D1;+0:11]):[c:12]>>[#7;a:7]:[c:8]:[c:9]:[c:10](-[NH;D2;+0:11]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])(-[C;D1;H3:5])-[C;D1;H3:6]):[c:12]
87
[{"value": 87.0, "product": "C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)NC(C(CC)(C)C)=O)C(CC)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.5, "product": "C1(CCCCC1)CN1C(=NC2=C1C=CC(=C2)NC(C(CC)(C)C)=O)C(CC)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
2,2-Dimethylbutyryl chloride (24.6 mg, 0.18 mmol) was added to a mixture of 1-(cyclohexylmethyl)-2-(1,1-dimethylpropyl)-1H-benzimidazol-5-amine hydrochloride (65.0 mg, 0.15 mmol) (for preparation see in Example 7, step B) and DMAP (73.3 mg, 0.60 mmol) in acetonitrile (5 mL) at 0° C. The mixture was stirred for 6 h at r...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccc2nc[nH]c2c1.C1CCCCC1
HCl
CN(C)C=1C=CN=CC1.C(C)#N.CCOC(=O)C
null
6
CCC(C)(C)C(=O)Cl.CCC(C)(C)c1nc2cc(N)ccc2n1CC1CCCCC1>CN(C)C=1C=CN=CC1.C(C)#N.CCOC(=O)C>CCC(C)(C)C(=O)Nc1ccc2c(c1)nc(C(C)(C)CC)n2CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d51432f38f2c4258983d49f9195f03f3
CC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1.CC(C)(C)C(=O)Cl>>CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
NC=1C=C(C=CC1NCC1CCCCC1)NC(C)=O.CC(C(=O)Cl)(C)C>>C(C)(C)(C)C1=NC2=C(N1CC1CCCCC1)C=CC(=C2)NC(C)=O
[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][cH:7][c:8]([NH:17][CH2:18][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)[c:9]([NH2:11])[cH:10]1.O=[C:12](Cl)[C:13]([CH3:14])([CH3:15])[CH3:16]>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][cH:7][c:8]2[c:9]([cH:10]1)[n:11][c:12]([C:13]([CH3:14])([CH3:15])[CH3:16])[n:17]2[CH2:18][CH:1...
CC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1.CC(C)(C)C(=O)Cl
CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
null
CN(C)C=1C=CN=CC1
ClCCl
Aromatic Heterocycle Formation
OtherReaction
b48b9f848f2f637750a62e12d0a60718d527408df46b4fc5f95f8aac64874f8d
56ef83dfadec35a1cf1db968b807e178cc4924ce15bf36d774883783cef0f450
c1ccc2c(c1)ncn2CC1CCCCC1
Cl-[C;H0;D3;+0:1](=O)-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5].[C:6]-[C:7]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11](-[NH2;D1;+0:12]):[c:13]>>[C:6]-[C:7]-[n;H0;D3;+0:8]1:[c:9](:[c:10]):[c:11](:[c:13]):[n;H0;D2;+0:12]:[c;H0;D3;+0:1]:1-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5]
72
[{"value": 72.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Following the same procedure of Example 6, a mixture of N-{3-amino-4-[(cyclohexylmethyl)amino]phenyl}acetamide (1.57 g, 6.0 mmol) (for preparation see in Example 6, step D) and DMAP (0.15 g, 1.2 mmol) in dichloromethane (70 mL) was treated with trimethylacetyl choride (0.83 g, 6.6 mmol) at −10° C. After evaporation of ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine.Secondary amine
null
c1ccccc1
c1ccc2nc[nH]c2c1
c1ccc2nc[nH]c2c1.C1CCCCC1
HCl
CN(C)C=1C=CN=CC1.ClCCl
null
null
CC(=O)Nc1ccc(NCC2CCCCC2)c(N)c1.CC(C)(C)C(=O)Cl>CN(C)C=1C=CN=CC1.ClCCl>CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5ee226211554458a9e908dd0753bfaf1
CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1.CI>>CC(=O)N(C)c1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
[H-].[Na+].C(C)(C)(C)C1=NC2=C(N1CC1CCCCC1)C=CC(=C2)NC(C)=O.IC>>C(C)(C)(C)C1=NC2=C(N1CC1CCCCC1)C=CC(=C2)N(C(C)=O)C
[CH3:1][C:2](=[O:3])[NH:4][c:6]1[cH:7][cH:8][c:9]2[c:10]([cH:11]1)[n:12][c:13]([C:14]([CH3:15])([CH3:16])[CH3:17])[n:18]2[CH2:19][CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1.I[CH3:5]>>[CH3:1][C:2](=[O:3])[N:4]([CH3:5])[c:6]1[cH:7][cH:8][c:9]2[c:10]([cH:11]1)[n:12][c:13]([C:14]([CH3:15])([CH3:16])[CH3:17])[n:18]2[C...
CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1.CI
CC(=O)N(C)c1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
780d850c4b8333c4b07101ff526eea0725c627f5cbcabe141bddc514762f1fac
0a16658309ac5595448433dd7ef49294830b145345df0b202ccd54727262e629
c1ccc2c(c1)ncn2CC1CCCCC1
I-[CH3;D1;+0:1].[#7;a:2]:[c:3]:[c:4]:[c:5](-[NH;D2;+0:6]-[C:7](-[C;D1;H3:8])=[O;D1;H0:9]):[c:10]>>[#7;a:2]:[c:3]:[c:4]:[c:5](-[N;H0;D3;+0:6](-[CH3;D1;+0:1])-[C:7](-[C;D1;H3:8])=[O;D1;H0:9]):[c:10]
100
[{"value": 100.0, "product": "C(C)(C)(C)C1=NC2=C(N1CC1CCCCC1)C=CC(=C2)N(C(C)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
Sodium hydride (201.5 mg, 5.04 mmol) was added to a solution of N-[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]acetamide (549.8 mg, 1.68 mmol) (for preparation see in Example 9) in THF (50 mL) at 0° C. Stirring for 30 min., iodomethane was added. The resulting mixture was stirred overnight at room temperatur...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Tertiary amide
null
null
c1ccc2nc[nH]c2c1.C1CCCCC1
HI
C1CCOC1
null
0.5
CC(=O)Nc1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1.CI>C1CCOC1>CC(=O)N(C)c1ccc2c(c1)nc(C(C)(C)C)n2CC1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6e11388875cb4d1e9dd3d37e11d95193
CC(C)(C)C(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1>>CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1
FC1=C(C=C(N)C=C1)[N+](=O)[O-].CC(C(=O)Cl)(C)C>>FC1=C(C=C(C=C1)NC(C(C)(C)C)=O)[N+](=O)[O-]
Cl[C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])=[O:6].[NH2:7][c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([N+:14](=[O:15])[O-:16])[cH:17]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[C:5](=[O:6])[NH:7][c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([N+:14](=[O:15])[O-:16])[cH:17]1
CC(C)(C)C(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1
CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1
null
CN(C)C=1C=CN=CC1
C(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[C;D1;H3:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C;D1;H3:4]-[C:3](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]
null
[]
null
null
3
HOUR
4-Fluoro-3-nitroaniline (500 mg, 3.20 mmol) and DMAP (586 mg, 4.80 mmol) were dissolved in 25 mL of DCM. Trimethylacetyl chloride (0.587 mL, 4.80 mmol) was added dropwise and the solution was stirred at rt for 3 h. The solution was washed with 5% KHSO4 solution, saturated NaHCO3 solution, brine and dried over anhydrous...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccccc1
HCl
CN(C)C=1C=CN=CC1.C(Cl)Cl
null
3
CC(C)(C)C(=O)Cl.Nc1ccc(F)c([N+](=O)[O-])c1>CN(C)C=1C=CN=CC1.C(Cl)Cl>CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-473ac90a2b0d4fa7a2f6d8d1489c704b
CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>>CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
FC1=C(C=C(C=C1)NC(C(C)(C)C)=O)[N+](=O)[O-].C1(CCCCC1)CN.C(C)N(CC)CC>>C1(CCCCC1)CNC1=C(C=C(C=C1)NC(C(C)(C)C)=O)[N+](=O)[O-]
F[c:11]1[cH:10][cH:9][c:8]([NH:7][C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])=[O:6])[cH:24][c:20]1[N+:21](=[O:22])[O-:23].[NH2:12][CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[C:5](=[O:6])[NH:7][c:8]1[cH:9][cH:10][c:11]([NH:12][CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]...
CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1
CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
null
null
CCO
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NCC2CCCCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[C:7]-[C:8]-[NH2;D1;+0:9]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[NH;D2;+0:9]-[C:8]-[C:7]):[c:2]:[c:3]
null
[]
null
null
null
null
N-(4-Fluoro-3-nitrophenyl)-2,2-dimethylpropanamide (158 mg, 0.658 mmol) and cyclohexylmethylamine (0.100 mL, 0.790 mmol) were stirred in 3 mL of EtOH containing triethylamine (0.140 mL, 0.987 mmol) at 75° C. for 24 h. The solvent was evaporated. The residue was dissolved in EtOAc and washed with 5% KHSO4 solution, satu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CCCCC1
HF
CCO
null
null
CC(C)(C)C(=O)Nc1ccc(F)c([N+](=O)[O-])c1.NCC1CCCCC1>CCO>CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-618390cab0f248739bb4b9165dc5860d
CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1>>CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
C1(CCCCC1)CNC1=C(C=C(C=C1)NC(C(C)(C)C)=O)[N+](=O)[O-]>>NC=1C=C(C=CC1NCC1CCCCC1)NC(C(C)(C)C)=O
O=[N+:21]([O-])[c:20]1[c:11]([NH:12][CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)[cH:10][cH:9][c:8]([NH:7][C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])=[O:6])[cH:22]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[C:5](=[O:6])[NH:7][c:8]1[cH:9][cH:10][c:11]([NH:12][CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)[c:20](...
CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1
CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
null
null
[Pd].CCOC(=O)C
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(NCC2CCCCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
24
HOUR
N-{4-[(Cyclohexylmethyl)amino]-3-nitrophenyl}-2,2-dimethylpropanamide (215 mg, 0.645 mmol) was dissolved in 20 mL of EtOAc containing a catalytic amount of 10% Pd/C. The solution was shaken in a Parr hydrogenation apparatus under H2 atmosphere (45 psi) at RT for 24 h. The solution was filtered through Celite and the so...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.C1CCCCC1
Other
[Pd].CCOC(=O)C
null
24
CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1>[Pd].CCOC(=O)C>CC(C)(C)C(=O)Nc1ccc(NCC2CCCCC2)c(N)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6e348835439b42cf93ab335a3b32cf69
CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2[nH]1.O=C(O)c1ccccc1-c1ccc(CBr)cc1>>CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
BrCC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)O.CN1C(=NC2=C1C=CC=C2)C2=CC1=C(N=C(N1)CCC)C(=C2)C.C(=O)([O-])[O-].[K+].[K+]>>CCCC1=NC2=C(C=C(C=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C(=O)OC)C5=NC6=CC=CC=C6N5C)C
[CH3:1][CH2:2][CH2:3][c:4]1[n:5][c:6]2[c:7]([CH3:8])[cH:9][c:10](-[c:11]3[n:12][c:13]4[cH:14][cH:15][cH:16][cH:17][c:18]4[n:19]3[CH3:20])[cH:21][c:22]2[nH:23]1.Br[CH2:24][c:25]1[cH:26][cH:27][c:28](-[c:29]2[cH:30][cH:31][cH:32][cH:33][c:34]2[C:35](=[O:36])[OH:37])[cH:39][cH:40]1>>[CH3:1][CH2:2][CH2:3][c:4]1[n:5][c:6]2[...
CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2[nH]1.O=C(O)c1ccccc1-c1ccc(CBr)cc1
CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
null
[Cl-].C[N+](CCCC)(CCCC)CCCC
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
OtherReaction
1695564f165c55ad3fbe70715b473f448c2f40815bd3cea3555039072c26d832
8446834f0edd1e71a2dcaffc09b80c7367abf3407263a8998354a2d20c1766bb
c1ccc(-c2ccc(Cn3cnc4ccc(-c5nc6ccccc6[nH]5)cc43)cc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6](-[OH;D1;+0:7])-[c:8].[C:9]-[c:10]1:[#7;a:11]:[c:12](:[c:13]):[c:14](:[c:15]):[nH;D2;+0:16]:1>>[C;D1;H3:17]-[O;H0;D2;+0:7]-[C:6](=[O;D1;H0:5])-[c:8].[C:9]-[c:10]1:[#7;a:11]:[c:12](:[c:13]):[c:14](:[c:15]):[n;H0;D3;+0:16]:1-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
72.3
[{"value": 69.0, "product": "CCCC1=NC2=C(C=C(C=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C(=O)OC)C5=NC6=CC=CC=C6N5C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.3, "product": "CCCC1=NC2=C(C=C(C=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C(=O)OC)C5=NC6=CC=CC=C6N5C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
87.5
CELSIUS
6
HOUR
1,7′-dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (BIM) (4 g), Aliquat® 175 (1.36 ml), K2CO3 (8.19 g), and toluene (50 ml) were added to a 250 ml round bottom flask equipped with a magnetic stirring bar and reflux condenser. The mixture was heated to reflux (about 85-90° C.) until a clear brown organic solution wa...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carboxylic acid
Ester
c1ccc2[nH]cnc2c1
c1ccc2[nH]cnc2c1
c1ccc2[nH]cnc2c1.c1nc2ccccc2[nH]1.c1ccccc1.c1ccccc1
null
[Cl-].C[N+](CCCC)(CCCC)CCCC.C1(=CC=CC=C1)C
87.5
6
CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2[nH]1.O=C(O)c1ccccc1-c1ccc(CBr)cc1>[Cl-].C[N+](CCCC)(CCCC)CCCC.C1(=CC=CC=C1)C>CCCc1nc2c(C)cc(-c3nc4ccccc4n3C)cc2n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-03e184bd9fb4474c9d96946be137c486
CC(C)(C)OC(=O)Nc1ccccc1N.COC(=O)c1ccc(C(=O)O)s1>>COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
C(=O)(N1C=NC=C1)N1C=NC=C1.COC(=O)C=1SC(=CC1)C(=O)O.C(C)(C)(C)OC(NC1=C(C=CC=C1)N)=O>>COC(=O)C=1SC(=CC1)C(NC1=C(C=CC=C1)NC(=O)OC(C)(C)C)=O
[NH2:11][c:12]1[cH:13][cH:14][cH:15][cH:16][c:17]1[NH:18][C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25].O[C:9]([c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[s:26]1)=[O:10]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[NH:18][C:19](=[O:20]...
CC(C)(C)OC(=O)Nc1ccccc1N.COC(=O)c1ccc(C(=O)O)s1
COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
null
null
C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccccc1)c1cccs1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#16;a:5]:[c:6]-[C:7](-[#8:8])=[O;D1;H0:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[#8:8]-[C:7](=[O;D1;H0:9])-[c:6]:[#16;a:5]:[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:4]
80.2
[{"value": 80.2, "product": "COC(=O)C=1SC(=CC1)C(NC1=C(C=CC=C1)NC(=O)OC(C)(C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
Under an argon atmosphere 21.0 g (129 mmol) carbonyldiimidazol was added to a solution of 24.1 g (129 mmol) thiophene-2,5-dicarboxylic acid monomethyl ester in 600 ml THF. After 2 h at rt 26.9 g (129 mmol) (2-amino-phenyl)-carbamic acid tert-butyl ester were added and the reaction mixture was stirred for further 4 h at...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccsc1.c1ccccc1
HO-
C1CCOC1
null
4
CC(C)(C)OC(=O)Nc1ccccc1N.COC(=O)c1ccc(C(=O)O)s1>C1CCOC1>COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b033aa5185934b6fbcdd9dcb079a7e3e
COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1>>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1
COC(=O)C=1SC(=CC1)C(NC1=C(C=CC=C1)NC(=O)OC(C)(C)C)=O.[OH-].[K+]>>C(C)(C)(C)OC(=O)NC1=C(C=CC=C1)NC(=O)C1=CC=C(S1)C(=O)O
C[O:24][C:22]([c:21]1[cH:20][cH:19][c:18]([C:16]([NH:15][c:14]2[c:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[cH:10][cH:11][cH:12][cH:13]2)=[O:17])[s:25]1)=[O:23]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[NH:15][C:16](=[O:17])[c:18]1[cH:19][cH:20][c:...
COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1
null
null
O.CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1ccccc1)c1cccs1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#16;a:5]>>[#16;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
80
[{"value": 80.0, "product": "C(C)(C)(C)OC(=O)NC1=C(C=CC=C1)NC(=O)C1=CC=C(S1)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
DAY
To a suspension of 18.5 g (50 mmol) 5-(2-tert-Butoxycarbonylamino-phenyl-carbamoyl)-thiophene-2-carboxylic acid methyl ester in 500 ml MeOH was added within 20 minutes a solution of 5.6 g (100 mmol) potassium hydroxide in 100 ml water. The reaction mixture was stirred at room temperature for 2 d. The MeOH was evaporate...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccsc1
Other
O.CO
null
48
COC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1>O.CO>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b076af4194334424a356e8ccd3dc643f
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1.CCCC(C)N>>CCCC(C)NC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
CC(CCC)N.C(C)(C)(C)OC(=O)NC1=C(C=CC=C1)NC(=O)C1=CC=C(S1)C(=O)O.C(=O)(N1C=NC=C1)N1C=NC=C1>>C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)C(NC(CCC)C)=O)=O
O[C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])[NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21]2[NH:22][C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[s:30]1.[CH3:1][CH2:2][CH2:3][CH:4]([CH3:5])[NH2:6]>>[CH3:1][CH2:2][CH2:3][CH:4]([CH3:5])[NH:6][C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])[N...
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1.CCCC(C)N
CCCC(C)NC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
null
null
C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccccc1)c1cccs1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#16;a:5]:[c:6]-[C:7](-[#7:8])=[O;D1;H0:9].[C:10]-[C:11](-[C;D1;H3:12])-[NH2;D1;+0:13]>>[#7:8]-[C:7](=[O;D1;H0:9])-[c:6]:[#16;a:5]:[c:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:13]-[C:11](-[C:10])-[C;D1;H3:12]):[c:4]
null
[]
45
CELSIUS
1
HOUR
To a solution of 4.4 g (12.1 mmol) 5-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-thiophene-2-carboxylic acid in 80 ml THF were added 2.2 g (13.6 mmol) carbonyldiimidazol. The reaction mixture was stirred at 45° C. for 1 h and then cooled to rt. After addition of 1.05 g (12 mmol) 2-pentylamine the reaction mixture was ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccsc1.c1ccccc1
HO-
C1CCOC1
45
1
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C(=O)O)s1.CCCC(C)N>C1CCOC1>CCCC(C)NC(=O)c1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-555416858ee142e9b821a504eebd6180
CC(C)N(CCN)C(C)C.COC(=O)c1ccc(C(=O)[O-])nc1>>COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1
COC(=O)C=1C=CC(=NC1)C(=O)[O-].[K+].S(=O)(Cl)Cl.C(C)(C)N(CCN)C(C)C.C(C)N(CC)CC>>COC(C1=CN=C(C=C1)C(NCCN(C(C)C)C(C)C)=O)=O
[NH2:11][CH2:12][CH2:13][N:14]([CH:15]([CH3:16])[CH3:17])[CH:18]([CH3:19])[CH3:20].[O-][C:9]([c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:22][n:21]1)=[O:10]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9](=[O:10])[NH:11][CH2:12][CH2:13][N:14]([CH:15]([CH3:16])[CH3:17])[CH:18]([CH3:19])[CH3:20])[n:21][c...
CC(C)N(CCN)C(C)C.COC(=O)c1ccc(C(=O)[O-])nc1
COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1
null
null
ClC(C)Cl.C(Cl)Cl.CN(C)C=O
Acylation
OtherReaction
01b411aa709aa72475efefee2037796aeb41c60940ddba8e15aefc45a95317a8
45ca336cc0b18cf59a837ab710e8845f67d23306b24bf1f37b36a34a2de4779a
c1ccncc1
[C:1]-[C:2]-[NH2;D1;+0:3].[O-]-[C;H0;D3;+0:4](=[O;D1;H0:5])-[c:6](:[c:7]):[#7;a:8]:[c:9]>>[C:1]-[C:2]-[NH;D2;+0:3]-[C;H0;D3;+0:4](=[O;D1;H0:5])-[c:6](:[c:7]):[#7;a:8]:[c:9]
74
[{"value": 74.0, "product": "COC(C1=CN=C(C=C1)C(NCCN(C(C)C)C(C)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
A suspension of 1.1 g (5 mmol) potassium 5-methoxycarbonyl-pyridine-2-carboxylate, 0.9 ml (12 mmol) thionyl chloride and 0.1 ml DMF in 5 ml dichloroethane was heated at reflux for 2 h. To the reaction mixture 5 ml CH2Cl2 were added and the solvent was evaporated. This procedure was repeated three times. The residue was...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Secondary amide
null
null
c1ccncc1
HO-
ClC(C)Cl.C(Cl)Cl.CN(C)C=O
null
12
CC(C)N(CCN)C(C)C.COC(=O)c1ccc(C(=O)[O-])nc1>ClC(C)Cl.C(Cl)Cl.CN(C)C=O>COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d4f71ddca79f434ca74141127ac04f8c
COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1>>CC(C)N(CCNC(=O)c1ccc(C(=O)O)cn1)C(C)C
COC(C1=CN=C(C=C1)C(NCCN(C(C)C)C(C)C)=O)=O.[OH-].[Na+]>>C(C)(C)N(CCNC(=O)C1=NC=C(C(=O)O)C=C1)C(C)C
C[O:16][C:14]([c:13]1[cH:12][cH:11][c:10]([C:8]([NH:7][CH2:6][CH2:5][N:4]([CH:2]([CH3:1])[CH3:3])[CH:19]([CH3:20])[CH3:21])=[O:9])[n:18][cH:17]1)=[O:15]>>[CH3:1][CH:2]([CH3:3])[N:4]([CH2:5][CH2:6][NH:7][C:8](=[O:9])[c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[OH:16])[cH:17][n:18]1)[CH:19]([CH3:20])[CH3:21]
COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1
CC(C)N(CCNC(=O)c1ccc(C(=O)O)cn1)C(C)C
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccncc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
88.9
[{"value": 88.9, "product": "C(C)(C)N(CCNC(=O)C1=NC=C(C(=O)O)C=C1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 1100 mg (3.6 mmol) 6-(2-diisopropylamino-ethylcarbamoyl)-nicotinic acid methyl ester in 10 ml THF and 3.0 ml MeOH was added 3.6 ml of an 2N aqueous NaOH solution. After 4 h at rt the solvent was evaporated. The residue was acidified with 1N HCl, filtered off and washed with water to give 936 mg (3.2 mm...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccncc1
Other
CO.C1CCOC1
null
null
COC(=O)c1ccc(C(=O)NCCN(C(C)C)C(C)C)nc1>CO.C1CCOC1>CC(C)N(CCNC(=O)c1ccc(C(=O)O)cn1)C(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6580ca4d42294055a46fcc7aa014cfdd
COC(=O)OC.O=C1CCc2cc(F)ccc2C1>>COC(=O)C1=C(O)CCc2cc(F)ccc21
C(C)(=O)O.[H-].[Na+].C(OC)(OC)=O.FC=1C=C2CCC(CC2=CC1)=O>>FC=1C=C2CCC(=C(C2=CC1)C(=O)OC)O
CO[C:3]([O:2][CH3:1])=[O:4].[CH2:5]1[C:6](=[O:7])[CH2:8][CH2:9][c:10]2[cH:11][c:12]([F:13])[cH:14][cH:15][c:16]21>>[CH3:1][O:2][C:3](=[O:4])[C:5]1=[C:6]([OH:7])[CH2:8][CH2:9][c:10]2[cH:11][c:12]([F:13])[cH:14][cH:15][c:16]21
COC(=O)OC.O=C1CCc2cc(F)ccc2C1
COC(=O)C1=C(O)CCc2cc(F)ccc21
null
null
O.C1(=CC=CC=C1)C
Acylation
OtherReaction
5d9c81ecf4037759bc3774402d21bcd515500b9416fbff21a1b406ba2c541e6c
a17e333db4ac4c45047cd486becf44e6d06842c4a345b2a174026b25ac18fe66
C1=Cc2ccccc2CC1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[O;H0;D1;+0:5]=[C;H0;D3;+0:6]1-[C:7]-[C:8]-[c:9]:[c:10](:[c:11])-[CH2;D2;+0:12]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:12]1=[C;H0;D3;+0:6](-[OH;D1;+0:5])-[C:7]-[C:8]-[c:9]:[c:10]-1:[c:11]
102.1
[{"value": 102.1, "product": "FC=1C=C2CCC(=C(C2=CC1)C(=O)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
12.66 g (316 mmol) of 60% sodium hydride in oil, 900 ml of toluene and 17.69 ml (210 mmol) of dimethyl carbonate are introduced into a 2 l reactor. The reaction mixture is stirred at reflux for 1 h. A solution of 19 g (115 mmol) of 6-fluoro-3,4-dihydro-1H-naphthalen-2-one in 350 ml of toluene is subsequently added. The...
10.6084/m9.figshare.5104873.v1
null
Carbonic Ester.Ketone
Ester.Enol
c1ccc2c(c1)CCCC2
C1=Cc2ccccc2CC1
C1=Cc2ccccc2CC1
HO-
O.C1(=CC=CC=C1)C
0
null
COC(=O)OC.O=C1CCc2cc(F)ccc2C1>O.C1(=CC=CC=C1)C>COC(=O)C1=C(O)CCc2cc(F)ccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-36ae9e63c57349b388155145f013119f
COC(=O)OC.O=C1CCc2cc(Cl)ccc2C1>>COC(=O)C1=C(O)CCc2cc(Cl)ccc21
C(C)(=O)O.[H-].[Na+].C(OC)(OC)=O.ClC=1C=C2CCC(CC2=CC1)=O>>ClC=1C=C2CCC(=C(C2=CC1)C(=O)OC)O
CO[C:3]([O:2][CH3:1])=[O:4].[CH2:5]1[C:6](=[O:7])[CH2:8][CH2:9][c:10]2[cH:11][c:12]([Cl:13])[cH:14][cH:15][c:16]21>>[CH3:1][O:2][C:3](=[O:4])[C:5]1=[C:6]([OH:7])[CH2:8][CH2:9][c:10]2[cH:11][c:12]([Cl:13])[cH:14][cH:15][c:16]21
COC(=O)OC.O=C1CCc2cc(Cl)ccc2C1
COC(=O)C1=C(O)CCc2cc(Cl)ccc21
null
null
O.C1(=CC=CC=C1)C
Acylation
OtherReaction
5d9c81ecf4037759bc3774402d21bcd515500b9416fbff21a1b406ba2c541e6c
a17e333db4ac4c45047cd486becf44e6d06842c4a345b2a174026b25ac18fe66
C1=Cc2ccccc2CC1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[O;H0;D1;+0:5]=[C;H0;D3;+0:6]1-[C:7]-[C:8]-[c:9]:[c:10](:[c:11])-[CH2;D2;+0:12]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:12]1=[C;H0;D3;+0:6](-[OH;D1;+0:5])-[C:7]-[C:8]-[c:9]:[c:10]-1:[c:11]
63.8
[{"value": 63.8, "product": "ClC=1C=C2CCC(=C(C2=CC1)C(=O)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
10.1 g (252 mmol) of 60% sodium hydride in oil, 621 ml of toluene and 14.18 ml (163 mmol) of dimethyl carbonate are introduced into a 2 l reactor. The reaction mixture is stirred at reflux for 1 h. A solution of 15.2 g (84 mmol) of 6-chloro-3,4-dihydro-1H-naphthalen-2-one in 268 ml of toluene is subsequently added. The...
10.6084/m9.figshare.5104873.v1
null
Carbonic Ester.Ketone
Ester.Enol
c1ccc2c(c1)CCCC2
C1=Cc2ccccc2CC1
C1=Cc2ccccc2CC1
HO-
O.C1(=CC=CC=C1)C
0
null
COC(=O)OC.O=C1CCc2cc(Cl)ccc2C1>O.C1(=CC=CC=C1)C>COC(=O)C1=C(O)CCc2cc(Cl)ccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-593b8763859d48099f2fdd0590072d81
COC(=O)OC.COc1ccc2c(c1)CC(=O)CC2>>COC(=O)C1=C(O)CCc2cc(OC)ccc21
C(C)(=O)O.[H-].[Na+].C(OC)(OC)=O.COC1=CC=C2CCC(CC2=C1)=O>>COC=1C=C2CCC(=C(C2=CC1)C(=O)OC)O
CO[C:3]([O:2][CH3:1])=[O:4].[CH2:5]1[C:6](=[O:7])[CH2:8][CH2:9][c:17]2[c:10]1[cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16]2>>[CH3:1][O:2][C:3](=[O:4])[C:5]1=[C:6]([OH:7])[CH2:8][CH2:9][c:10]2[cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16][c:17]21
COC(=O)OC.COc1ccc2c(c1)CC(=O)CC2
COC(=O)C1=C(O)CCc2cc(OC)ccc21
null
null
O.C1(=CC=CC=C1)C.C(Cl)Cl.CCCCCCC
Acylation
OtherReaction
5d9c81ecf4037759bc3774402d21bcd515500b9416fbff21a1b406ba2c541e6c
a17e333db4ac4c45047cd486becf44e6d06842c4a345b2a174026b25ac18fe66
C1=Cc2ccccc2CC1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[O;H0;D1;+0:5]=[C;H0;D3;+0:6]1-[C:7]-[CH2;D2;+0:8]-[c;H0;D3;+0:9]2:[c:10]:[c:11]:[c:12]:[c:13]:[c;H0;D3;+0:14]:2-[CH2;D2;+0:15]-1>>[C;D1;H3:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:15]1=[C;H0;D3;+0:6](-[OH;D1;+0:5])-[C:7]-[CH2;D2;+0:8]-[c;H0;D3;+0:14]2:[c:13...
null
[]
0
CELSIUS
null
null
3.4 g (85.12 mmol) of 60% sodium hydride in oil, 180 ml of toluene and 4.78 ml (56.75 mmol) of dimethyl carbonate are introduced into a 1 l reactor. The reaction mixture is stirred at reflux for 1 h. A solution of 5 g (28.37 mmol) of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one in 100 ml of toluene is subsequently added. ...
10.6084/m9.figshare.5104873.v1
null
Carbonic Ester.Ketone
Ester.Enol
c1ccc2c(c1)CCCC2
C1=Cc2ccccc2CC1
C1=Cc2ccccc2CC1
HO-
O.C1(=CC=CC=C1)C.C(Cl)Cl.CCCCCCC
0
null
COC(=O)OC.COc1ccc2c(c1)CC(=O)CC2>O.C1(=CC=CC=C1)C.C(Cl)Cl.CCCCCCC>COC(=O)C1=C(O)CCc2cc(OC)ccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5adedddb5d9c4d5195e95bda36137964
CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2c1-c1ccc(Cl)cc1CC2)C(C)C>>CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2ccc3cc(Cl)ccc3c12)C(C)C.Cl
C(C)(C)N(C(OC1=NN(C=2CCC3=C(C12)C=CC(=C3)Cl)C3=CC=NC=C3)=O)C(C)C.BrN1C(CCC1=O)=O.N(=NC(C#N)(C)C)C(C#N)(C)C>>Cl.C(C)(C)N(C(OC1=NN(C=2C=CC3=C(C12)C=CC(=C3)Cl)C3=CC=NC=C3)=O)C(C)C
[CH3:1][CH:2]([CH3:3])[N:4]([C:5](=[O:6])[O:7][c:8]1[n:9][n:10](-[c:11]2[cH:12][cH:13][n:14][cH:15][cH:16]2)[c:17]2[c:27]1-[c:26]1[c:20]([cH:21][c:22]([Cl:23])[cH:24][cH:25]1)[CH2:19][CH2:18]2)[CH:28]([CH3:29])[CH3:30]>>[CH3:1][CH:2]([CH3:3])[N:4]([C:5](=[O:6])[O:7][c:8]1[n:9][n:10](-[c:11]2[cH:12][cH:13][n:14][cH:15][...
CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2c1-c1ccc(Cl)cc1CC2)C(C)C
CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2ccc3cc(Cl)ccc3c12)C(C)C.Cl
null
null
Cl.C(C)(C)O.C(Cl)(Cl)(Cl)Cl
Miscellaneous
OtherReaction
090fe45c3b84079cbdfd7b82e205a304c6ad82109b20fd38e0a4c736d914bfda
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
c1ccc2c(c1)ccc1c2cnn1-c1ccncc1
[#7:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[c:5]1:[#7;a:6]:[#7;a:7](-[c:8]):[c:9]2:[c;H0;D3;+0:10]:1-[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:14](:[c:15])-[CH2;D2;+0:16]-[CH2;D2;+0:17]-2>>[#7:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[c:5]1:[#7;a:6]:[#7;a:7](-[c:8]):[c:9]2:[cH;D2;+0:17]:[cH;D2;+0:16]:[c:14](:[c:15]):[c;H0;D3;+0:11](:[c:12]:[c:13...
153.8
[{"value": 153.8, "product": "Cl.C(C)(C)N(C(OC1=NN(C=2C=CC3=C(C12)C=CC(=C3)Cl)C3=CC=NC=C3)=O)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1.65 g (3.38 mmol) of 7-chloro-4,5-dihydro-3-(pyrid-4-yl)-3H-benzo[e]indazol-1-yl N,N-diisopropylcarbamate, prepared according to the method described in Example 5, 1.105 g (6.21 mmol) of N-bromosuccinimide and 0.127 g (0.78 mmol) of 2,2′-azobis(2-methylpropionitrile) are added to a 100 ml reactor. The mixture, dissolv...
10.6084/m9.figshare.5104873.v1
null
null
null
c1ccc2c(c1)CCc1n[nH]cc12
c1ccc2c(c1)ccc1n[nH]cc12
c1ccncc1.c1ccc2c(c1)ccc1n[nH]cc12
Other
Cl.C(C)(C)O.C(Cl)(Cl)(Cl)Cl
null
null
CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2c1-c1ccc(Cl)cc1CC2)C(C)C>Cl.C(C)(C)O.C(Cl)(Cl)(Cl)Cl>CC(C)N(C(=O)Oc1nn(-c2ccncc2)c2ccc3cc(Cl)ccc3c12)C(C)C.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3654749bd2124ffea1d495cab9ceb180
CN(CCO)Cc1ccccc1>>CN(CC=O)Cc1ccccc1
N1=CC=CC=C1.S(=O)(=O)=O.C(C1=CC=CC=C1)N(CCO)C.CCN(C(C)C)C(C)C.CS(=O)C>>C(C1=CC=CC=C1)N(C)CC=O
[CH3:1][N:2]([CH2:3][CH2:4][OH:5])[CH2:6][c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1>>[CH3:1][N:2]([CH2:3][CH:4]=[O:5])[CH2:6][c:7]1[cH:8][cH:9][cH:10][cH:11][cH:12]1
CN(CCO)Cc1ccccc1
CN(CC=O)Cc1ccccc1
null
null
C(Cl)Cl
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
c1ccccc1
[#7:1]-[C:2]-[CH2;D2;+0:3]-[OH;D1;+0:4]>>[#7:1]-[C:2]-[CH;D2;+0:3]=[O;H0;D1;+0:4]
null
[]
-10
CELSIUS
2
HOUR
To a 3-necked 2-L flask was added N-benzyl-N-methylethanolamine (30.5 g, 0.182 mol), DCM (0.5 L), DIPEA (95 mL, 0.546 mol) and DMSO (41 mL, 0.728 mol). Using an ice bath, the mixture was cooled to about −10° C. and sulfur trioxide pyridine-complex (87 g, 0.546 mol) was added in 4 portions over 5 minute intervals. The r...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
c1ccccc1
null
C(Cl)Cl
-10
2
CN(CCO)Cc1ccccc1>C(Cl)Cl>CN(CC=O)Cc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-835950a0473148e2ba014fda33faac7f
COC(OC)N(C)C.Nc1nc(Br)cnc1Br>>CN(C)C=Nc1nc(Br)cnc1Br
BrC=1C(=NC(=CN1)Br)N.COC(N(C)C)OC>>BrC=1C(=NC(=CN1)Br)N=CN(C)C
CO[CH:4](OC)[N:2]([CH3:1])[CH3:3].[NH2:5][c:6]1[n:7][c:8]([Br:9])[cH:10][n:11][c:12]1[Br:13]>>[CH3:1][N:2]([CH3:3])[CH:4]=[N:5][c:6]1[n:7][c:8]([Br:9])[cH:10][n:11][c:12]1[Br:13]
COC(OC)N(C)C.Nc1nc(Br)cnc1Br
CN(C)C=Nc1nc(Br)cnc1Br
null
null
C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
0d701f00585e4f39a6a7fc9a495a6e4c12bb39eb0ddc06ef90888eddc323e4b7
e5ad6b21478dc075562b413728aa025da8232f58653a7afd9501cb514659723b
c1cnccn1
C-O-[CH;D3;+0:1](-O-C)-[#7:2](-[C;D1;H3:3])-[C;D1;H3:4].[Br;D1;H0:5]-[c:6]1:[#7;a:7]:[c:8]:[c:9]:[#7;a:10]:[c:11]:1-[NH2;D1;+0:12]>>[Br;D1;H0:5]-[c:6]1:[#7;a:7]:[c:8]:[c:9]:[#7;a:10]:[c:11]:1-[N;H0;D2;+0:12]=[CH;D2;+0:1]-[#7:2](-[C;D1;H3:3])-[C;D1;H3:4]
99.3
[{"value": 99.3, "product": "BrC=1C(=NC(=CN1)Br)N=CN(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 3,6-dibromo-pyrazin-2-ylamine (15.37 g, 60.80 mmol) and N,N-dimethylformamide dimethyl acetal (10.1 mL, 76.00 mmol), suspended in ethanol (150 mL), is refluxed for 2 hours. The reaction mixture is evaporated in vacuo affording the title compound (18.6 g). 1H-NMR (400 MHz, CDCl3) δ(ppm) 3.20 (s, 3H), 3.21 (...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Primary amine
null
null
null
c1cnccn1
HO-
C(C)O
null
null
COC(OC)N(C)C.Nc1nc(Br)cnc1Br>C(C)O>CN(C)C=Nc1nc(Br)cnc1Br
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1e737b89f157485b802b28ad6ae009a4
CN(C)C=Nc1nc(Br)cnc1Br.NO>>ON=CNc1nc(Br)cnc1Br
BrC=1C(=NC(=CN1)Br)N=CN(C)C.Cl.NO>>BrC=1C(=NC(=CN1)Br)NC=NO
CN(C)[CH:3]=[N:4][c:5]1[n:6][c:7]([Br:8])[cH:9][n:10][c:11]1[Br:12].[OH:1][NH2:2]>>[OH:1][N:2]=[CH:3][NH:4][c:5]1[n:6][c:7]([Br:8])[cH:9][n:10][c:11]1[Br:12]
CN(C)C=Nc1nc(Br)cnc1Br.NO
ON=CNc1nc(Br)cnc1Br
null
null
CO
Heteroatom Alkylation and Arylation
OtherReaction
9c6166fd7e5a817bf213fd9daccfae72f646d2b10a52b5122c4c1be4856f9ac0
ecd935dc844075fc6e2817ede9c8c1363134a018b1e26143e72f4dc910dff438
c1cnccn1
C-N(-C)-[CH;D2;+0:1]=[N;H0;D2;+0:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[#7;a:7]:[c:8]:1-[Br;D1;H0:9].[NH2;D1;+0:10]-[O;D1;H1:11]>>[Br;D1;H0:9]-[c:8]1:[#7;a:7]:[c:6]:[c:5]:[#7;a:4]:[c:3]:1-[NH;D2;+0:2]-[CH;D2;+0:1]=[N;H0;D2;+0:10]-[O;D1;H1:11]
97
[{"value": 97.0, "product": "BrC=1C(=NC(=CN1)Br)NC=NO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of N′-(3,6-dibromo-pyrazin-2-yl)-N,N-dimethylformamidine (18.6 g, 60.80 mmol) in methanol (200 mL) is added hydroxylamine hydrochloride (5.91 g, 85.12 mmol) in one portion. The reaction is stirred at room temperature for 16 hours. The solvent is evaporated and the solid residue is treated with cold (ice c...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Tertiary amine
Secondary amine.Oxime
null
null
c1cnccn1
Other
CO
null
16
CN(C)C=Nc1nc(Br)cnc1Br.NO>CO>ON=CNc1nc(Br)cnc1Br
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8435ddd943c94774ab8a007e9038c22c
ON=CNc1nc(Br)cnc1Br>>Brc1ncc(Br)n2ncnc12
BrC=1C(=NC(=CN1)Br)NC=NO.C(=O)(O)[O-].[Na+]>>BrC1=CN=C(C=2N1N=CN2)Br
O[N:8]=[CH:9][NH:10][c:11]1[c:2]([Br:1])[n:3][cH:4][c:5]([Br:6])[n:7]1>>[Br:1][c:2]1[n:3][cH:4][c:5]([Br:6])[n:7]2[n:8][cH:9][n:10][c:11]12
ON=CNc1nc(Br)cnc1Br
Brc1ncc(Br)n2ncnc12
null
null
O
Aromatic Heterocycle Formation
OtherReaction
1fa44d6fb59f874198f0796e8eb1848cb936176048c11601bbc53c105abaffc3
c1d239b36a16d8c63e1df13f889e3523ec358c146b56c8c2a09aa8afeeaad4d2
c1cn2ncnc2cn1
O-[N;H0;D2;+0:1]=[CH;D2;+0:2]-[NH;D2;+0:3]-[c:4]1:[n;H0;D2;+0:5]:[c:6](-[Br;D1;H0:7]):[c:8]:[#7;a:9]:[c:10]:1-[Br;D1;H0:11]>>[Br;D1;H0:11]-[c:10]1:[#7;a:9]:[c:8]:[c:6](-[Br;D1;H0:7]):[n;H0;D3;+0:5]2:[n;H0;D2;+0:1]:[cH;D2;+0:2]:[n;H0;D2;+0:3]:[c:4]:1:2
62.1
[{"value": 62.1, "product": "BrC1=CN=C(C=2N1N=CN2)Br", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.75
HOUR
N-(3,6-dibromo-pyrazin-2-yl)-N′-hydroxyformamidine (17.4 mg, 58.80 mmol) is treated with polyphosphoric acid (150 g) for one hour at 50° C. and then for 1.75 hours at 70° C. After cooling to room temperature, water is added to the reaction mixture. The resultant suspension is brought to pH 8 by careful addition of soli...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Oxime
null
c1cnccn1
c1cn2ncnc2cn1
c1cn2ncnc2cn1
HO-
O
null
1.75
ON=CNc1nc(Br)cnc1Br>O>Brc1ncc(Br)n2ncnc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3027a9cb758e4615b7dfccaa86d4073f
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)cc1>>Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12
BrC1=CN=C(C=2N1N=CN2)Br.C1COCCN1C2=CC=C(C=C2)N.C(C)N(C(C)C)C(C)C>>BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2
Br[c:5]1[n:4][cH:3][c:2]([Br:1])[n:23]2[c:19]1[n:20][cH:21][n:22]2.[NH2:6][c:7]1[cH:8][cH:9][c:10]([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[cH:17][cH:18]1>>[Br:1][c:2]1[cH:3][n:4][c:5]([NH:6][c:7]2[cH:8][cH:9][c:10]([N:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[cH:17][cH:18]2)[c:19]2[n:20][cH:21][n:22][n:23]12
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)cc1
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12
null
null
CC(C)O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
aecfb0ede2c5d7901fea69101287828edf21f7a6e48b6ff83fe43de0688f1ef1
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cn2ncnc2c(Nc2ccc(N3CCOCC3)cc2)n1
Br-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1.[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1):[c:13]
94
[{"value": 94.0, "product": "BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.8, "product": "BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 5,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (123 mg, 443 μmol), 4-(4-morpholino)aniline (118 mg. 0.664 mmol) and N-ethyldiisopropylamine (116 mL, 0.664 mmol) is heated at reflux in 2-propanol (3 mL) for 4.5 hours. The reaction mixture is evaporated to dryness and the residue partitioned between dichlorometh...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cn2ncnc2cn1
c1cn2ncnc2cn1
c1ccccc1.C1COCC[NH]1.c1cn2ncnc2cn1
HBr
CC(C)O
null
null
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)cc1>CC(C)O>Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-36290199d22b4ef481537591340ea0ba
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.COc1cc(B(O)O)ccn1>>COc1cc(-c2cnc(Nc3ccc(N4CCN(C)CC4)cc3)c3ncnn23)ccn1
C(=O)([O-])[O-].[Na+].[Na+].BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C.COC1=NC=CC(=C1)B(O)O>>COC1=NC=CC(=C1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C
Br[c:6]1[cH:7][n:8][c:9]([NH:10][c:11]2[cH:12][cH:13][c:14]([N:15]3[CH2:16][CH2:17][N:18]([CH3:19])[CH2:20][CH2:21]3)[cH:22][cH:23]2)[c:24]2[n:25][cH:26][n:27][n:28]12.OB(O)[c:5]1[cH:4][c:3]([O:2][CH3:1])[n:31][cH:30][cH:29]1>>[CH3:1][O:2][c:3]1[cH:4][c:5](-[c:6]2[cH:7][n:8][c:9]([NH:10][c:11]3[cH:12][cH:13][c:14]([N:1...
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.COc1cc(B(O)O)ccn1
COc1cc(-c2cnc(Nc3ccc(N4CCN(C)CC4)cc3)c3ncnn23)ccn1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
CN(C)C=O.O1CCOCC1
C-C Coupling
Suzuki coupling with boronic acids
5d08686f43da8e30538f859764d1c446b3e676ebc229f2d3adde0518ff14c3b0
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1cc(-c2cnc(Nc3ccc(N4CCNCC4)cc3)c3ncnn23)ccn1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:2:1.O-B(-O)-[c;H0;D3;+0:10]1:[c:11]:[c:12]:[#7;a:13]:[c:14](-[#8:15]):[c:16]:1>>[#8:15]-[c:14]1:[#7;a:13]:[c:12]:[c:11]:[c;H0;D3;+0:10](-[c;H0;D3;+0:1]2:[c:2]:[#7;a:3]:[c:4]:[c:5]3:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:3:2):[c:16]:1
47
[{"value": 47.0, "product": "COC1=NC=CC(=C1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.6, "product": "COC1=NC=CC(=C1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (80 mg, 0.206 mmol), 2-methoxypyridine-4-boronic acid (63 mg, 0.412 mmol), Pd(PPh3)4 (0.052 mmol) and 1.5N Na2CO3 (1.1 mL, 1.65 mmol) in 2:1 DMF/d...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1cn2ncnc2cn1.c1ccncc1
c1ccncc1.c1cn2ncnc2cn1
c1ccncc1.c1ccccc1.C1C[NH]CC[NH]1.c1cn2ncnc2cn1
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.CN(C)C=O.O1CCOCC1
null
null
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.COc1cc(B(O)O)ccn1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.CN(C)C=O.O1CCOCC1>COc1cc(-c2cnc(Nc3ccc(N4CCN(C)CC4)cc3)c3ncnn23)ccn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-142319d9b5d94c9b8cb3e693faf50430
Brc1ncc(Br)n2ncnc12.CN1CCN(c2ccc(N)cc2)CC1>>CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1
BrC1=CN=C(C=2N1N=CN2)Br.CN1CCN(CC1)C1=CC=C(C=C1)N.C(C)N(C(C)C)C(C)C>>BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C
Br[c:11]1[n:12][cH:13][c:14]([Br:15])[n:16]2[n:17][cH:18][n:19][c:20]12.[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[cH:7][cH:8][c:9]([NH2:10])[cH:21][cH:22]2)[CH2:23][CH2:24]1>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[cH:7][cH:8][c:9]([NH:10][c:11]3[n:12][cH:13][c:14]([Br:15])[n:16]4[n:17][cH:18][n:19][c:20]34)[cH:21][cH:22...
Brc1ncc(Br)n2ncnc12.CN1CCN(c2ccc(N)cc2)CC1
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1
null
null
CC(C)O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
aecfb0ede2c5d7901fea69101287828edf21f7a6e48b6ff83fe43de0688f1ef1
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cn2ncnc2c(Nc2ccc(N3CCNCC3)cc2)n1
Br-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1.[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1):[c:13]
50.4
[{"value": 50.4, "product": "BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 5,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (2 g, 7.20 mmol), 4-(4-methyl-piperazin-1-yl)-phenylamine (1.65 g, 8.64 mmol) and N-ethyldiisopropyl-amine (1.5 mL, 8.64 mmol) is heated at 80° C. in 2-propanol (50 mL) for 8 hours. The reaction mixture is evaporated to dryness and the residue partitioned between ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cn2ncnc2cn1
c1cn2ncnc2cn1
C1C[NH]CC[NH]1.c1ccccc1.c1cn2ncnc2cn1
HBr
CC(C)O
null
null
Brc1ncc(Br)n2ncnc12.CN1CCN(c2ccc(N)cc2)CC1>CC(C)O>CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bf0b15a623a643ca8612d5bf1a657bbb
O=C(O)c1sccc1Br>>NC(=O)c1cc(Br)cs1
BrC1=C(SC=C1)C(=O)O.Cl.C(C)N=C=NCCCN(C)C.O.ON1N=NC2=C1C=CC=C2.O>>BrC=1C=C(SC1)C(=O)N
O[C:2](=[O:3])[c:4]1[c:6]([Br:7])[cH:5][cH:8][s:9]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([Br:7])[cH:8][s:9]1
O=C(O)c1sccc1Br
NC(=O)c1cc(Br)cs1
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
88c98fffcc34d527a612bb0d59e9cb29f690664f80d146dcce3712eb24cd731f
5714ff853ee51aa1194ed7b37a31c645a0cb082d2b538f94dd2497088a2eecf7
c1ccsc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c;H0;D3;+0:3]1:[#16;a:4]:[cH;D2;+0:5]:[cH;D2;+0:6]:[c;H0;D3;+0:7]:1-[Br;D1;H0:8]>>[Br;D1;H0:8]-[c;H0;D3;+0:7]1:[cH;D2;+0:6]:[c;H0;D3;+0:3](-[C;H0;D3;+0:1](-[N;D1;H2:9])=[O;D1;H0:2]):[#16;a:4]:[cH;D2;+0:5]:1
78
[{"value": 78.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
5
HOUR
A solution of 4 bromo-thiophene-2-carboxylic acid (2.0 g, 9.66 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (2.04 g, 10.63 mmol) and 1-hydroxybenzotriazole hydrate (1.44 g, 10.63 mmol) in DMF (20 mL) is stirred at room temperature for 2 hours. The reaction mixture is then cooled to 0° C. and aq. ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carboxylic acid
Aromatic halide.Primary amide
c1ccsc1
c1ccsc1
c1ccsc1
null
CN(C)C=O
0
5
O=C(O)c1sccc1Br>CN(C)C=O>NC(=O)c1cc(Br)cs1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-44cfe51f98c9404a98626aa029bb074a
N.O=C(O)c1ccc(Br)s1>>NC(=O)c1ccc(Br)s1
N.BrC1=CC=C(S1)C(=O)O.O.ON1N=NC2=C1C=CC=C2.C(C)N=C=NCCCN(C)C>>BrC1=CC=C(S1)C(=O)N
[NH3:1].O[C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7]([Br:8])[s:9]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7]([Br:8])[s:9]1
N.O=C(O)c1ccc(Br)s1
NC(=O)c1ccc(Br)s1
null
null
CN(C)C=O
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
c1ccsc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#16;a:5]:[c:6].[NH3;D0;+0:7]>>[NH2;D1;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#16;a:5]:[c:6]
84.2
[{"value": 84.0, "product": "BrC1=CC=C(S1)C(=O)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.2, "product": "BrC1=CC=C(S1)C(=O)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
8
HOUR
A solution of 5-bromo-thiophene-2-carboxylic acid (4.51 g, 21.78 mmol), 3-hydroxybenzotriazole hydrate (3.24 g, 23.96 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (4.6 g, 23.96 mmol) in DMF (70 mL) is stirred at room temperature for 2 hours. The reaction mixture is then cooled to 0° C. and aq. 35% NH3 (2.2 mL)...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccsc1
HO-
CN(C)C=O
0
8
N.O=C(O)c1ccc(Br)s1>CN(C)C=O>NC(=O)c1ccc(Br)s1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-27d59b0c73f54c99a026e5b3704acb56
CC1(C)OB(c2ccc(C(N)=O)s2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>>CN1CCN(c2ccc(Nc3ncc(-c4ccc(C(N)=O)s4)n4ncnc34)cc2)CC1.N
CC1(OB(OC1(C)C)C1=CC=C(S1)C(=O)N)C.CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.C(=O)([O-])[O-].[Na+].[Na+].CN1CCN(CC1)C1=CC=C(C=C1)N>>N.CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C1=CC=C(S1)C(=O)N)N=CN2
CC1(C)OB(c2[cH:16][cH:17][c:18]([C:19]([NH2:20])=[O:21])[s:22]2)OC1(C)C.O=C(c1c[c:15](-[c:14]2[cH:13][n:12][c:11]([NH:10][c:9]3[cH:8][cH:7][c:6]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:31][CH2:30]4)[cH:29][cH:28]3)[c:27]3[n:23]2[n:24][cH:25][n:26]3)cs1)[NH2:32]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[cH:7][cH:8][c:9]([...
CC1(C)OB(c2ccc(C(N)=O)s2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1
CN1CCN(c2ccc(Nc3ncc(-c4ccc(C(N)=O)s4)n4ncnc34)cc2)CC1.N
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1
Miscellaneous
OtherReaction
7c91011d7ca932b4650404ee0f5c9c5b345e30ce123b75474c550eb6fcfd4df2
f3f7f26bbd316ddb41ef1d9256d6e3eab68cee0318289c68e4524d92797ff759
c1csc(-c2cnc(Nc3ccc(N4CCNCC4)cc3)c3ncnn23)c1
C-C1(-C)-O-B(-c2:[cH;D2;+0:1]:[c:2]:[c:3](-[C:4](-[N;D1;H2:5])=[O;D1;H0:6]):[s;H0;D2;+0:7]:2)-O-C-1(-C)-C.O=C(-[NH2;D1;+0:8])-c1:c:[c;H0;D3;+0:9](-[c:10]2:[c:11]:[#7;a:12]:[c:13]:[c:14]3:[#7;a:15]:[c:16]:[#7;a:17]:[#7;a:18]:2:3):c:s:1>>[N;D1;H2:5]-[C:4](=[O;D1;H0:6])-[c:3]1:[c:2]:[cH;D2;+0:1]:[c;H0;D3;+0:9](-[c:10]2:[c...
21
[{"value": 21.0, "product": "CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C1=CC=C(S1)C(=O)N)N=CN2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using 5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (100 mg, 0.258 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxa-borolan-2-yl)-thiophene-2-carboxylic acid amide (130 mg, 0.516 mmol) and Pd(PPh3)4 (74 mg...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Boronic ester
null
B1OCCO1.c1ccsc1.c1ccsc1
c1ccsc1
C1C[NH]CC[NH]1.c1ccccc1.c1ccsc1.c1cn2ncnc2cn1
B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1
null
null
CC1(C)OB(c2ccc(C(N)=O)s2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1>CN1CCN(c2ccc(Nc3ncc(-c4ccc(C(N)=O)s4)n4ncnc34)cc2)CC1...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1be6752f028e44bf8d127f68b503efe8
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1>>Cc1[nH]ncc1-c1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.N
CC1=C(C=NN1)B1OC(C(O1)(C)C)(C)C.CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.C(=O)([O-])[O-].[Na+].[Na+].BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2>>N.CC1=C(C=NN1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2
Br[c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][c:15]([N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[cH:22][cH:23]2)[c:24]2[n:25][cH:26][n:27][n:28]12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(=O)[NH2:29])c4)n4ncnc34)cc2)CC1.CC1(C)OB([c:6]2[c:2]([CH3:1])[nH:3][n:4][cH:5]2)OC1(C)C>>[CH3:1][c:2]1[nH:3][n:4][cH:5][c:6]1-[c:7]1...
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1
Cc1[nH]ncc1-c1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.N
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1
C-C Coupling
OtherReaction
5450a2db6e7305c45383870e931e62f9935b44015cf383067240af8b2a416783
96e5f3628c1bd4659dd3e9821904115decf673d0e8e42bb7900b7f521b084c51
c1nc2c(Nc3ccc(N4CCOCC4)cc3)ncc(-c3cn[nH]c3)n2n1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:2:1.C-C1(-C)-O-B(-[c;H0;D3;+0:10]2:[c:11]:[#7;a:12]:[#7;a:13]:[c:14]:2-[C;D1;H3:15])-O-C-1(-C)-C.C-N1-C-C-N(-c2:c:c:c(-N-c3:n:c:c(-c4:c:s:c(-C(=O)-[NH2;D1;+0:16]):c:4):n4:n:c:n:c:3:4):c:c:2)-C-C-1>>[C;D1;H3:15]-[c:14]1:[#7;a:13]:[#7;a:12]:[...
7.5
[{"value": 7.5, "product": "CC1=C(C=NN1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-yl-phenyl)-amine (0.2 g, 0.53 mmol), 5-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (222 mg, 1.06 mmol), and Pd(PPh3)4 (0.154 mg, 0.134 mmol) in 1.5M N...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amide.Secondary amine.Tertiary amine.Tertiary amine.Boronic ester
null
c1cn2ncnc2cn1.C1CNCCN1.c1ccccc1.c1ccsc1.c1cn2ncnc2cn1.B1OCCO1.c1cn[nH]c1
c1cn[nH]c1.c1cn2ncnc2cn1
c1cn[nH]c1.c1ccccc1.C1COCC[NH]1.c1cn2ncnc2cn1
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1
null
null
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1>Cc1[nH]ncc1-c1cnc(...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e824f0d68eec45008eaf33f03d3aea81
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>>NC(=O)c1cc(-c2cnc(Nc3ccc(N4CCOCC4)cc3)c3ncnn23)cs1
C(=O)([O-])[O-].[Na+].[Na+].CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCOCC2.CC1(OB(OC1(C)C)C=1C=C(SC1)C(=O)N)C>>N1(CCOCC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2
Br[c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][c:15]([N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[cH:22][cH:23]2)[c:24]2[n:25][cH:26][n:27][n:28]12.CN1CCN(c2ccc(Nc3ncc(-[c:6]4[cH:5][c:4]([C:2]([NH2:1])=[O:3])[s:30][cH:29]4)n4ncnc34)cc2)CC1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][c:6](-[c:7]2[cH:8][n:9][c:10]([NH:1...
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1
NC(=O)c1cc(-c2cnc(Nc3ccc(N4CCOCC4)cc3)c3ncnn23)cs1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1
C-C Coupling
OtherReaction
611105c70cffe68ca772f63b3c7585081a4d3c0cedb754af02c62b3e48eb31ea
29d6ca637af3bedb92e90114efa267a3e4e226d46d2cbc04aef1a3fdafc7a7e3
c1nc2c(Nc3ccc(N4CCOCC4)cc3)ncc(-c3ccsc3)n2n1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:2:1.C-N1-C-C-N(-c2:c:c:c(-N-c3:n:c:c(-[c;H0;D3;+0:10]4:[c:11]:[#16;a:12]:[c:13](-[C:14](-[N;D1;H2:15])=[O;D1;H0:16]):[c:17]:4):n4:n:c:n:c:3:4):c:c:2)-C-C-1>>[N;D1;H2:15]-[C:14](=[O;D1;H0:16])-[c:13]1:[#16;a:12]:[c:11]:[c;H0;D3;+0:10](-[c;H0...
37.4
[{"value": 37.4, "product": "N1(CCOCC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-yl-phenyl)-amine (0.2 g, 0.53 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxylic acid amide (0.27 mg, 1.06 mmol), and Pd(PPh3)4 (0.15 mg, 0.133 mm...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine.Tertiary amine.Tertiary amine
null
c1cn2ncnc2cn1.C1CNCCN1.c1ccccc1.c1ccsc1.c1cn2ncnc2cn1
c1ccsc1.c1cn2ncnc2cn1
c1ccsc1.c1ccccc1.C1COCC[NH]1.c1cn2ncnc2cn1
HBr
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1
null
null
Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1>NC(=O)c1cc(-c2cnc(Nc3ccc(N4CCOCC4)cc3)c3ncnn23)cs...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f0e66e2bb47948cd888b49e707892845
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1>>Cc1[nH]ncc1-c1cnc(Nc2ccc(N3CCN(C)CC3)cc2)c2ncnn12
C(=O)([O-])[O-].[Na+].[Na+].CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.BrC1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C.CC1=C(C=NN1)B1OC(C(O1)(C)C)(C)C>>CC1=C(C=NN1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C
Br[c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][c:15]([N:16]3[CH2:17][CH2:18][N:19]([CH3:20])[CH2:21][CH2:22]3)[cH:23][cH:24]2)[c:25]2[n:26][cH:27][n:28][n:29]12.CC1(C)OB([c:6]2[c:2]([CH3:1])[nH:3][n:4][cH:5]2)OC1(C)C>>[CH3:1][c:2]1[nH:3][n:4][cH:5][c:6]1-[c:7]1[cH:8][n:9][c:10]([NH:11][c:12]2[cH:13][cH:14][c:15...
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1
Cc1[nH]ncc1-c1cnc(Nc2ccc(N3CCN(C)CC3)cc2)c2ncnn12
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1
C-C Coupling
Suzuki coupling with boronic esters
3b077e58a8068174133a7eecad35957570f9290725408c31a955826b02d2e470
b42efb3b6a7742d5af594c6a3031e487327e58e9f8c2f428ee68996c98377910
c1nc2c(Nc3ccc(N4CCNCC4)cc3)ncc(-c3cn[nH]c3)n2n1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:2:1.C-C1(-C)-O-B(-[c;H0;D3;+0:10]2:[c:11]:[#7;a:12]:[#7;a:13]:[c:14]:2-[C;D1;H3:15])-O-C-1(-C)-C>>[C;D1;H3:15]-[c:14]1:[#7;a:13]:[#7;a:12]:[c:11]:[c;H0;D3;+0:10]:1-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]...
7
[{"value": 7.0, "product": "CC1=C(C=NN1)C1=CN=C(C=2N1N=CN2)NC2=CC=C(C=C2)N2CCN(CC2)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (132 mg, 0.340 mmol), 5-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (141 mg, 0.68 mmol), Pd(PPh3)4 (98 mg, 0.085 mmol) and...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic ester
null
c1cn2ncnc2cn1.B1OCCO1.c1cn[nH]c1
c1cn[nH]c1.c1cn2ncnc2cn1
c1cn[nH]c1.c1ccccc1.C1C[NH]CC[NH]1.c1cn2ncnc2cn1
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1
null
null
CN1CCN(c2ccc(Nc3ncc(Br)n4ncnc34)cc2)CC1.Cc1[nH]ncc1B1OC(C)(C)C(C)(C)O1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1>Cc1[nH]ncc1-c1cnc(Nc2ccc(N3CCN(C)CC3)cc2)c2ncnn12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-785ca2cd5f0f4662b415f70122108024
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)c(F)c1>>Fc1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
CCN(C(C)C)C(C)C.CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.BrC1=CN=C(C=2N1N=CN2)Br.FC=1C=C(C=CC1N1CCOCC1)N>>BrC1=CN=C(C=2N1N=CN2)NC2=CC(=C(C=C2)N2CCOCC2)F
Br[c:6]1[n:7][cH:8][c:9]([Br:10])[n:11]2[n:12][cH:13][n:14][c:15]12.[F:1][c:2]1[cH:3][c:4]([NH2:5])[cH:16][cH:17][c:18]1[N:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1>>[F:1][c:2]1[cH:3][c:4]([NH:5][c:6]2[n:7][cH:8][c:9]([Br:10])[n:11]3[n:12][cH:13][n:14][c:15]23)[cH:16][cH:17][c:18]1[N:19]1[CH2:20][CH2:21][O:22][CH2:23...
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)c(F)c1
Fc1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
null
null
CC(C)O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
aecfb0ede2c5d7901fea69101287828edf21f7a6e48b6ff83fe43de0688f1ef1
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cn2ncnc2c(Nc2ccc(N3CCOCC3)cc2)n1
Br-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1.[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1):[c:13]
98.5
[{"value": 98.0, "product": "BrC1=CN=C(C=2N1N=CN2)NC2=CC(=C(C=C2)N2CCOCC2)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.5, "product": "BrC1=CN=C(C=2N1N=CN2)NC2=CC(=C(C=C2)N2CCOCC2)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 1 using 5,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (0.5 g, 1.799 mmol), 3-fluoro-4-morpholin-4-yl-phenylamine (0.53 g, 2.70 mmol), and DIPEA (0.470 mL, 2.70 mmol) in 2-propanol (6 mL). The reaction mixture is partitioned between 10% citric ac...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cn2ncnc2cn1
c1cn2ncnc2cn1
c1ccccc1.c1cn2ncnc2cn1.C1COCC[NH]1
HBr
CC(C)O
null
null
Brc1ncc(Br)n2ncnc12.Nc1ccc(N2CCOCC2)c(F)c1>CC(C)O>Fc1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-abcfc0fd01024e77a4fdc5b5948e1eb0
Brc1ncc(Br)n2ncnc12.CC(C)O.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>>NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.BrC1=CN=C(C=2N1N=CN2)Br.CCOCC.CC(C)O.CC(C)O.C(C)(C)N(C(C)C)CC>>BrC1=CN=C(C=2N1N=CN2)NC=2C=CC(=C(C(=O)N)C2)N2CCOCC2
Br[c:8]1[n:9][cH:10][c:11]([Br:12])[n:13]2[n:14][cH:15][n:16][c:17]12.CC(C)[OH:24].CN1[CH2:23][CH2:22][N:21]([c:20]2cc[c:6]([NH:7]c3ncc(-c4cs[c:4]([C:2]([NH2:1])=[O:3])[cH:5]4)n4ncnc34)[cH:18][cH:19]2)[CH2:26][CH2:25]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][c:8]2[n:9][cH:10][c:11]([Br:12])[n:13]3[n:14][cH:15][n:...
Brc1ncc(Br)n2ncnc12.CC(C)O.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1
NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
f24be8ea534e9125d766fcfc3db0d39d1570189087ed9b240d08fee6ed445d29
93b1adaa9fdf847e37e9437ec2849798bd990e21a9ad5ba2bd6bd1346eaa708d
c1cn2ncnc2c(Nc2ccc(N3CCOCC3)cc2)n1
Br-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:1.C-C(-C)-[OH;D1;+0:10].C-N1-[CH2;D2;+0:11]-[C:12]-[#7:13](-[c;H0;D3;+0:14]2:[c:15]:[c:16]:[c;H0;D3;+0:17](-[NH;D2;+0:18]-c3:n:c:c(-c4:[cH;D2;+0:19]:[c;H0;D3;+0:20](-[C:21](-[N;D1;H2:22])=[O;D1;H0:23]):s:c:4):n4:n:c:n:c:3:4):c:c:2)-[C:24]...
73
[{"value": 73.0, "product": "BrC1=CN=C(C=2N1N=CN2)NC=2C=CC(=C(C(=O)N)C2)N2CCOCC2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 1 using 5,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (250 mg, 0.90 mmol) 5-amino-2-morpholin-4-yl benzamide (299 mg, 1.35 mmol) and N,N-diisopropylethylamine (0.24 mL, 1.35 mmol) in 2-propanol (7 mL). Trituration with iPrOH and Et2O affords the...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary alcohol.Secondary amine.Tertiary amine
Ether.Secondary amine
c1cn2ncnc2cn1.C1CNCC[NH]1.c1ccccc1.c1ccsc1.c1cn2ncnc2cn1
c1ccccc1.c1cn2ncnc2cn1.C1COCC[NH]1
c1ccccc1.c1cn2ncnc2cn1.C1COCC[NH]1
HBr
null
null
null
Brc1ncc(Br)n2ncnc12.CC(C)O.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1>>NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6c6efd22323b4263a477df3bd1120f0d
CC1(C)OB(c2cn[nH]c2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1>>N.NC(=O)c1cc(Nc2ncc(-c3cn[nH]c3)n3ncnc23)ccc1N1CCOCC1
CC1(OB(OC1(C)C)C=1C=NNC1)C.CN1CCN(CC1)C1=CC=C(C=C1)NC=1C=2N(C(=CN1)C=1C=C(SC1)C(=O)N)N=CN2.BrC1=CN=C(C=2N1N=CN2)NC=2C=CC(=C(C(=O)N)C2)N2CCOCC2>>N.N1N=CC(=C1)C1=CN=C(C=2N1N=CN2)NC=2C=CC(=C(C(=O)N)C2)N2CCOCC2
CC1(C)OB([c:13]2[cH:14][n:15][nH:16][cH:17]2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(=O)[NH2:1])c4)n4ncnc34)cc2)CC1.Br[c:12]1[cH:11][n:10][c:9]([NH:8][c:7]2[cH:6][c:5]([C:3]([NH2:2])=[O:4])[c:25]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[cH:24][cH:23]2)[c:22]2[n:18]1[n:19][cH:20][n:21]2>>[NH3:1].[NH2:2][C:3](=[O:4])...
CC1(C)OB(c2cn[nH]c2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1
N.NC(=O)c1cc(Nc2ncc(-c3cn[nH]c3)n3ncnc23)ccc1N1CCOCC1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]
C-C Coupling
OtherReaction
5450a2db6e7305c45383870e931e62f9935b44015cf383067240af8b2a416783
96e5f3628c1bd4659dd3e9821904115decf673d0e8e42bb7900b7f521b084c51
c1nc2c(Nc3ccc(N4CCOCC4)cc3)ncc(-c3cn[nH]c3)n2n1
Br-[c;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7]:[#7;a:8]:[#7;a:9]:2:1.C-C1(-C)-O-B(-[c;H0;D3;+0:10]2:[c:11]:[#7;a:12]:[#7;a:13]:[c:14]:2)-O-C-1(-C)-C.C-N1-C-C-N(-c2:c:c:c(-N-c3:n:c:c(-c4:c:s:c(-C(=O)-[NH2;D1;+0:15]):c:4):n4:n:c:n:c:3:4):c:c:2)-C-C-1>>[#7;a:3]1:[c:2]:[c;H0;D3;+0:1](-[c;H0;D3;+0:10]2:[c:11]...
30
[{"value": 30.0, "product": "N1N=CC(=C1)C1=CN=C(C=2N1N=CN2)NC=2C=CC(=C(C(=O)N)C2)N2CCOCC2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
This compound may be prepared using methods as described for Compound 6, step 4 using 5-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-2-morpholin-4-yl-benzamide (140 mg, 0.33 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (130 mg, 0.67 mmol) and Pd(PPh3)4 (96 mg, 0.083 mmol) in 1.5M K2CO3 (aq) ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amide.Secondary amine.Tertiary amine.Tertiary amine.Boronic ester
null
B1OCCO1.c1cn[nH]c1.C1CNCCN1.c1ccccc1.c1ccsc1.c1cn2ncnc2cn1.c1cn2ncnc2cn1
c1cn[nH]c1.c1cn2ncnc2cn1
c1ccccc1.c1cn[nH]c1.c1cn2ncnc2cn1.C1COCC[NH]1
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]
null
null
CC1(C)OB(c2cn[nH]c2)OC1(C)C.CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1.NC(=O)c1cc(Nc2ncc(Br)n3ncnc23)ccc1N1CCOCC1>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O1CCOCC1.C(=O)([O-])[O-]...