tert-Butanol → Tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 1779027노트

반응식

HRID 1779027 반응식
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.CC(O)(C)C.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:26])=[CH:21][CH:20]=1.CCN(CC)CC>[Cl-].[Cl-].[Zn+2].ClCCCl>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:26])=[CH:21][CH:20]=2)[N:7]=1

참가 물질

7

반응물 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 22569414tert-butyl N-[1-(4-aminophenyl)ethyl]carbamate

생성물 1

HCID 76611269Tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

시약·촉매·용매 2

HCID 3007855Zincchloride촉매HCID 111,2-Dichloroethane용매

실험 절차

ZnCl2 (1.0 M in Et2O; 3.27 mL, 3.27 mmol) was added to a stirred solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (620 mg, 2.86 mmol) in a 1:1 t-BuOH:DCE mixture (120 mL) at room temperature. After stirring for 20 minutes tert-butyl 1-(4-aminophenyl)ethylcarbamate (0.643 g, 2.72 mmol) (prepared according to Bioorganic and Medicinal Chemistry Letters, 14(7), 1751-1755; 2004) followed by Et3N (455 μL, 3.27 mmol) was added and the resulting mixture stirred at room temperature overnight. The volatiles were evaporated to dryness and the resulting residue purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-10% EtOAc in cyclohexane) to give the title compound A63 (480 mg, 42%); 1H NMR (300 MHz, CDCl3) δ 8.57 (s, 1H), 7.56 (m, 1H), 7.56 (d, J=8.61 Hz, 2H), 7.33 (d, J=8.61 Hz, 2H), 4.81 (m, 2H), 1.46 (m, 12H). LCMS-B: rt 8.47 min; m/z 417 [M+H]+.

후처리

  1. customat room temperature
  2. additionwas added
  3. customThe volatiles were evaporated to dryness
  4. customthe resulting residue purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-10% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-cd15a2c4580f4a9f8e37674d68d9ab35
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266864B2

반응 노트

불러오는 중…