Ethyl Acetate → GDC-0994

HRID 1774207노트

반응식

HRID 1774207 반응식
[Si]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]3[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=3)[N:26]=2)=[CH:21][CH2:20]1)[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)(C(C)(C)C)(C)C.C(OCC)(=[O:40])C>>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:10]([N:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]4[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=4)[N:26]=3)=[CH:21][C:20]2=[O:40])[CH2:9][OH:8])=[CH:12][C:13]=1[F:18]

참가 물질

3

반응물 2

HCID 8857Ethyl Acetate2회HCID 86731991HCID 86731991, 화합물

생성물 1

HCID 71727581GDC-0994수율 54.6%

실험 절차

Crude (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H-one (48 mg) was dissolved in ethyl acetate (4 mL) and treated dropwise slowly (over 2 minutes) with an ethyl acetate solution (1.0 mL, which had been saturated with HCl gas). The reaction stirred at room temperature for 15 minutes, after which time LCMS indicated complete consumption of the starting material. The reaction mixture was concentrated to an oily residue and purified by prep RP HPLC to yield (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (20.8 mg, 54.6% yield) as a lyophilized powder. 1H NMR (400 MHz, (CD3)2SO) δ 9.58 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 7.91 (t, J=9.0 Hz, 1H), 7.58 (t, J=8.1 Hz, 1H), 7.52-7.41 (m, 2H), 7.37 (d, J=1.8 Hz, 1H), 7.14 (dd, J=10.7, 5.1 Hz 2H), 6.86 (dd, J=7.3, 1.8 Hz, 1H), 6.27 (d, J=1.7 Hz, 1H), 5.97 (dd, J=7.7, 5.7 Hz, 1H), 5.31 (t, J=5.2 Hz, 1H), 4.15 (m, 1H), 4.10-3.95 (m, 1H), 3.69 (s, 3H); LCMS m/z 441 (M+H)+.

후처리

  1. customconsumption of the starting material
  2. concentrationThe reaction mixture was concentrated to an oily residue
  3. custompurified by prep RP HPLC

출처 및 근거

ORD 기록
ord-9ffcbaa5dc764c93bfdfc02c764ccd51
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09259470B2

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