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

HRID 507033노트

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HRID 507033 반응식
[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

참가 물질

5

반응물 3

HCID 10476Cyanogen BromideHCID 81531DiisopropylethylamineHCID 59432291(S)-tert-butyl 5-(3,5-bistrifluoromethylbenzylamino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

생성물 1

HCID 59432409(S)-tert-butyl 5-[(3,5-bistrifluoromethylbenzyl)cyanoamino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate수율 99%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

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)+.

후처리

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

출처 및 근거

ORD 기록
ord-3efcb9e45beb4338835b4fcd565dfc8d
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786108B2

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