Diisopropylethylamine → {1-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester

HRID 71787노트

반응식

HRID 71787 반응식
Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[O:5].[C:13]([O:17][C:18]([NH:20][C:21]1([C:24](O)=[O:25])[CH2:23][CH2:22]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C:21]1([C:24](=[O:25])[NH:2][CH2:3][C:4]([C:6]2[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=2)=[O:5])[CH2:22][CH2:23]1)([CH3:16])([CH3:14])[CH3:15]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

생성물 1

HCID 66620021{1-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester수율 90%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

2-Amino-1-(4-bromo-phenyl)-ethanone HCl (2.5 g, 10 mmol) in DMF (30 mL) was treated with 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid (1.97 g, 9.8 mmol), HATU (4.02 g, 10.5 mmol), and DIPEA (5.6 mL, 31.1 mmol). The mixture was stirred for 18 hours and concentrated. The mixture was diluted with EtOAc (25 mL), and washed with saturated NaHCO3 (310 mL), H2O (10 mL), and brine (10 mL). The solution was dried over MgSO4 and subjected to a 80 g SiO2 COMBIFLASH column (0-100% EtOAc-hexanes gradient) to afford {1-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester (3.49 g, 90%). This material (3.49 g, 8.8 mmol) in xylenes (20 mL) was treated with ammonium acetate (3.4 g, 44 mmol). The reaction was stirred at 130° C. in a sealed tube for 18 hours. The mixture was concentrated and suspended in dicholormethane (100 mL) and washed with saturated NaHCO3 (50 mL). The solution was dried over MgSO4 to afford crude {1-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-cyclopropyl}-carbamic acid tert-butyl ester, which was used without further purification: MS (ESI) m/z 379 [M+H]+.

후처리

  1. concentrationconcentrated
  2. additionThe mixture was diluted with EtOAc (25 mL)
  3. washwashed with saturated NaHCO3 (310 mL), H2O (10 mL), and brine (10 mL)
  4. dry with materialThe solution was dried over MgSO4

출처 및 근거

ORD 기록
ord-9b4f398ba0d24c08bb9266cc65ba7cb9
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822430B2

반응 노트

불러오는 중…