Potassium Carbonate → (R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl ester

HRID 1896095노트

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HRID 1896095 반응식
[O:1]=[C:2]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=[C:25]2[CH2:24]1)[CH2:3][C@H:4]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].[Br:36]N1C(=O)CCC1=O.C(=O)([O-])[O-].[K+].[K+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(O)C>[O:1]=[C:2]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:33])([F:34])[F:35])=[N:30][C:31]([Br:36])=[C:25]2[CH2:24]1)[CH2:3][C@H:4]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14]

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 90495Di-tert-butyl dicarbonateHCID 57518397(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl ester

생성물 1

HCID 57518400(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl ester수율 86.3%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

tert-Butyl(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1m (20.0 g, 39.6 mmol) was dissolved in 300 mL of anhydrous ethanol, and N-bromosuccinimide (14.1 g, 79.2 mmol) was then added to the solution. After stirring for an hour, potassium carbonate (10.9 g, 79.2 mmol) and di-tert-butyl dicarbonate (8.6 g, 39.6 mmol) were added to the mixture, and the mixture was stirred for another one hour. The reaction mixture was filtered through a pad of coarse silica gel, and then the filtrate was concentrated under reduced pressure. The resulting residues were purified by silica gel column chromatography with system B as eluant to obtain the title compound tert-butyl (R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1n (20.0 g, yield 86%) as a white solid. 1HNMR (400 MHz, CDCl3, ppm): δ 7.063 (m, 1H), 6.88 (m, 1H), 4.72 (s, 1H), 4.56 (s, 1H), 4.13 (m, 3H), 3.88 (m, 2H), 2.94 (m, 2H), 2.62 (m, 2H), 1.36 (s, 9H).

후처리

  1. stirringthe mixture was stirred for another one hour
  2. filtrationThe reaction mixture was filtered through a pad of coarse silica gel
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resulting residues were purified by silica gel column chromatography with system B as eluant

출처 및 근거

ORD 기록
ord-172513d7867a4b82a536fc679719b71a
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518946B2

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