Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 3-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamide

HRID 1041803Notes

Reaction equation

HRID 1041803 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][N:10]([CH3:12])[CH2:9][C:8](=[O:13])[NH:7][C:6]=2[CH:14]=1.[CH3:15][NH:16][C:17]([C:19]1[S:20][CH:21]=[C:22]([CH3:33])[C:23]=1[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[C:27](Cl)[N:26]=1)=[O:18].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(O)C>[CH3:15][NH:16][C:17]([C:19]1[S:20][CH:21]=[C:22]([CH3:33])[C:23]=1[NH:24][C:25]1[C:30]([Cl:31])=[CH:29][N:28]=[C:27]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][N:10]([CH3:12])[CH2:9][C:8](=[O:13])[NH:7][C:6]=3[CH:14]=2)[N:26]=1)=[O:18]

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 672638558-Amino-4-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-oneHCID 866340193-(2,5-dichloropyrimidin-4-ylamino)-N,4-dimethylthiophene-2-carboxamide

Product 1

HCID 251590103-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamideYield 3.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 8-amino-4-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (25 mg, 0.13 mmol), 3-(2,5-dichloro-pyrimidin-4-ylamino)-4-methyl-thiophene-2-carboxylic acid methylamide (49.6 mg, 0.16 mmol), and camphorsulfonic acid (33 mg, 0.13 mmol) were heated in IPA (3 mL) at 120° C. for 16 hours. Concentration and chromatography on preparative TLC with methylene chloride and methanol (100:8) gave 2.1 mg of 3-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamide (3.4%): 1H NMR (300 MHz, CD3OD) δ 8.1 (d, 1H), 7.98 (s, 1H), 7.7 (m, 1H), 7.35 (m, 2H), 7.15 (s, 1H), 3.65 (s, 1H), 3.61 (s, 1H), 3.2 (s, 2H), 2.85 (s, 3H), 2.52 (s, 3H), 2.1 (s, 3H); MS (m/e): 472.2 (M+1).

Workup

  1. concentrationConcentration and chromatography on preparative TLC with methylene chloride and methanol (100:8)

Sources & evidence

ORD record
ord-5374f7c95bff44408dca612dc4c66c62
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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