Ethyl Acetate → (2R)-2-(3-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-3H-benzo[d]imidazol-5-ylamino)-2-(4-fluorophenyl)ethanol

HRID 1092213노트

반응식

HRID 1092213 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:11][OH:12])=[C:4]([F:20])[C:3]=1[NH:21][C:22]1[CH:26]=[C:25]([CH:27]2[CH2:29][CH2:28]2)[NH:24][N:23]=1.[C:30](O)(=O)C.C(N)=N.C(=O)(O)[O-].[Na+].CCOC(C)=O>CCO>[CH:27]1([C:25]2[NH:24][N:23]=[C:22]([N:21]3[C:3]4[C:4]([F:20])=[C:5]([NH:9][C@H:10]([C:13]5[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=5)[CH2:11][OH:12])[C:6]([F:8])=[CH:7][C:2]=4[N:1]=[CH:30]3)[CH:26]=2)[CH2:29][CH2:28]1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 86621764(R)-2-(4-Amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluorophenylamino)-2-(4-fluorophenyl)ethanol

생성물 1

HCID 66589182(2R)-2-(3-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-3H-benzo[d]imidazol-5-ylamino)-2-(4-fluorophenyl)ethanol

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

(R)-2-(4-Amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluorophenylamino)-2-(4-fluorophenyl)ethanol (Method 104, 0.230 g, 0.57 mmol) and formamidine acetate (0.119 g, 1.14 mmol) in EtOH (10 ml) was heated at reflux for 1 hour. Saturated sodium bicarbonate solution (5 ml) and EtOAc (15 ml) were added. The organic layer was separated, washed with brine (3 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by chromatography (Hex-EtOAc=1:1) to give the title compound as off white solid (0.070 g, 30%). 1H NMR (400 MHz) 12.83 (s, 1H), 8.20 (s, 1H), 7.34 (m, 3H), 7.07 (t, J=8.8 Hz, 2H), 6.14 (s, 1H), 5.14 (d, J=9.6 Hz, 1H), 4.97 (t, J=5.6 Hz, 1H), 4.62 (m, 1H), 3.64-3.74 (m, 2H), 1.97 (m, 1H), 1.00 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 413; Found: [M+H]+ 414.

후처리

  1. temperatureat reflux for 1 hour
  2. customThe organic layer was separated
  3. washwashed with brine (3 ml)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by chromatography (Hex-EtOAc=1:1)

출처 및 근거

ORD 기록
ord-4be7594dfdb14f5e9998281da16dac14
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129403B2

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