Benzodiazepine → HCID 67060852, compound

HRID 1186096Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=2[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:6](=[O:9])[CH2:7][N:8]=1.CC(C)([O-])C.[K+].N1C2C=CC=CC=2C=CC=N1.[Cl:41][C:42]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:43]=1[CH2:44]Br>O1CCCC1>[Cl:1][C:2]1[C:3]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=2[N:5]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)[C:6](=[O:9])[CH:7]([CH2:44][C:43]2[CH:46]=[CH:47][C:48]([F:50])=[CH:49][C:42]=2[Cl:41])[N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

5,7-Dichloro-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.85 g, 3.82 mmol) was dissolved in anhydrous tetrahydrofuran (15 mL) and cooled to −78° C. under nitrogen. Potassium tert-butoxide (0.48 g, 3.82 mmol) was dissolved in anhydrous tetrahydrofuran (4 mL) and added to the benzodiazepine via syringe. After 2 minutes, a solution of the 2-chloro-4-fluorobenzyl bromide (1.27 g, 3.64 mmol) in anhydrous tetrahydrofuran (3 mL) was added. The reaction mixture was stirred at −78° C. for 2 then allowed to warm to room temperature over 1 h. The reaction was quenched with water and the layers partitioned. The organic layer was evaporated onto silica gel and chromatographed eluting with 10-35% ethyl acetate in hexanes to obtain 5,7-dichloro-3-(2-chloro-4-fluorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.6 g, 1.22 mmol).

Workup

temperatureto warm to room temperature over 1 h
customThe reaction was quenched with water
customthe layers partitioned
customThe organic layer was evaporated onto silica gel
customchromatographed
washeluting with 10-35% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-7f23d60c8eb34af89b7d6be19df22c1e
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673897B2

Reaction notes

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