Aluminum(III) Chloride → 7-Chloro-3-(2-chlorophenethyl)-5-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1910686Notes

Reaction equation

[Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:30])[CH:8]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:12]=[C:13]4[NH:19][C:18](=[O:20])[NH:17][C:14]4=[N:15][CH:16]=3)[C:4]=2[CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C1(OC)C=CC=CC=1>[Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[NH:6][C:7](=[O:30])[CH:8]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:12]=[C:13]4[NH:19][C:18](=[O:20])[NH:17][C:14]4=[N:15][CH:16]=3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

7-Chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-5-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (50 mg) was dissolved in anisole (2.1 mL) and aluminum chloride (46 mg, 4 eq) was added. The reaction was stirred at 85° C. for 2 h, then poured into ice:EtOAc (1:1). The quenched reaction was stirred vigorously for 1 h, then the organic layer was separated, washed with brine, dried over sodium sulfate, and then concentrated onto silica gel and purified by chromatography (gradient: DCM to 9:1 DCM:MeOH) delivering product (10 mg, 25% yield). HRMS (ES+) m/z calcd for C23H17Cl2N5O2 [M+H]+, 466.0838. found, 466.0838.

Workup

customThe quenched reaction
stirringwas stirred vigorously for 1 h
customthe organic layer was separated
washwashed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated onto silica gel
custompurified by chromatography (gradient: DCM to 9:1 DCM:MeOH)

Sources & evidence

ORD record: ord-94beeb80edf54cf6bdfae8db6f689a31
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08604023B2

Reaction notes

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