Cyanogen Bromide → (S)-tert-butyl 5-[(3,5-bistrifluoromethylbenzyl)cyanoamino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 507033Notes

Reaction equation

[N:1]#[C:2]Br.[F:4][C:5]([F:42])([F:41])[C:6]1[CH:7]=[C:8]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:9][NH:10][C@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]2[CH:25]=[C:26]([C:30]([F:33])([F:32])[F:31])[C:27]([CH3:29])=[CH:28][C:12]1=2.C(N(C(C)C)CC)(C)C>O1CCCC1>[F:42][C:5]([F:4])([F:41])[C:6]1[CH:7]=[C:8]([CH:34]=[C:35]([C:37]([F:39])([F:38])[F:40])[CH:36]=1)[CH2:9][N:10]([C:2]#[N:1])[C@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[C:13]2[CH:25]=[C:26]([C:30]([F:33])([F:31])[F:32])[C:27]([CH3:29])=[CH:28][C:12]1=2

Participants

Conditions

Temperature: 50 °C

Procedure

Add cyanogen bromide (1.21 mL, 6.04 mmol, 5 M solution in acetonitrile) to a solution of (S)-tert-butyl 5-(3,5-bistrifluoromethylbenzylamino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (2.30 g, 4.03 mmol) and diisopropylethylamine (1.05 mL, 6.04 mmol) in tetrahydrofuran (50 mL) at room temperature under nitrogen and heat the mixture at 50° C. for 12 h. Add silica gel to the cooled mixture and remove the solvents under reduced pressure. Purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (2:3), to provide the title compound as a colorless oil (2.10 g, >99%), which is used in the next step without further purification: APCI MS m/z 496 (M+H−Boc)+.

Workup

customAdd silica gel to the cooled mixture and remove the solvents under reduced pressure
customPurify the residue by column chromatography on silica gel
washeluting with ethyl acetate/hexanes (2:3)

Sources & evidence

ORD record: ord-3efcb9e45beb4338835b4fcd565dfc8d
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786108B2

Reaction notes

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