Water → 8-Chloro-7-dimethylamino-4-[3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one

HRID 1265921Notes

Reaction equation

[Cl:1][C:2]1[C:3]([N:27]([CH3:29])[CH3:28])=[CH:4][C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]4[S:19][CH:20]=[C:21]([CH2:23]Cl)[N:22]=4)[CH:13]=3)[CH2:9][C:8](=[O:25])[NH:7][C:6]=2[CH:26]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.O>CCO>[Cl:1][C:2]1[C:3]([N:27]([CH3:28])[CH3:29])=[CH:4][C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]4[S:19][CH:20]=[C:21]([CH2:23][N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)[N:22]=4)[CH:13]=3)[CH2:9][C:8](=[O:25])[NH:7][C:6]=2[CH:26]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 8-chloro-4-[3-(4-chloromethyl-thiazol-2-yl)-phenyl]-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one (89 mg) (Example 191a), morpholine (0.17 mL) and KI (3 mg) in EtOH (0.5 mL) was stirred at 60° C. for 3 h. H2O (25 mL) was added to the cooled solution and the precipitate was collected by filtration and purified by chromatography on silica gel using AcOEt/acetone (1:1) as eluent. The product was stirred with 20% aqueous MeOH (20 mL) The pH of the mixture was set to 11 by addition of 1N NaOH and the solid was subsequently isolated by filtration to give the title compound (55 mg) as yellow powder.

Workup

filtrationthe precipitate was collected by filtration
custompurified by chromatography on silica gel
stirringThe product was stirred with 20% aqueous MeOH (20 mL) The pH of the mixture
additionwas set to 11 by addition of 1N NaOH
customthe solid was subsequently isolated by filtration

Sources & evidence

ORD record: ord-61fbf06fc0964867b60510e5a7f73b28
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06544985B2

Reaction notes

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