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Acetic Acid → 1-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}-N,N-dimethylpiperidine-4-carboxamide diformate

HRID 426078
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HRID 426078 반응식
[N:1]1([C:5]([CH:7]2[CH2:12][CH2:11][N:10]([CH:13]3[CH2:16][N:15]([CH2:17][CH2:18][C@@H:19]([C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[CH2:20][N:21]([CH3:35])[C:22](=[O:34])[C:23]4[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([Br:33])[CH:24]=4)[CH2:14]3)[CH2:9][CH2:8]2)=[O:6])[CH2:4]C[CH2:2]1.N1CC(N2CCC(C(N(C)C)=O)CC2)C1.[C:58]([OH:61])(=[O:60])C>CO>[CH:58]([OH:61])=[O:60].[CH:58]([OH:61])=[O:60].[Br:33][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:26]=1)[C:22]([N:21]([CH3:35])[CH2:20][C@H:19]([C:36]1[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=1)[CH2:18][CH2:17][N:15]1[CH2:14][CH:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:5]([N:1]([CH3:2])[CH3:4])=[O:6])[CH2:8][CH2:9]2)[CH2:16]1)=[O:34]
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참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 23582759N-[(2S)-4-{3-[4-(Azetidin-1-ylcarbonyl)piperidin-1-yl]azetidin-1-yl}-2-(4-fluorophenyl)butyl]-3-bromo-N-methyl-5-(trifluoromethyl)benzamideHCID 236587821-azetidin-3-yl-N,N-dimethylpiperidine-4-carboxamide

생성물 1

HCID 866165021-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}-N,N-dimethylpiperidine-4-carboxamide diformate수율 77%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A mixture of 3-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see method 1; 0.178 g, 0.40 mmol), 1-azetidin-3-yl-N,N-dimethylpiperidine-4-carboxamide (see method 3; 0.084 g, 0.40 mmol), acetic acid (0.3 mL), (polystyrylmethyl)trimethylammonium cyanoborohydride (0.098 g, 0.52 mmol) and methanol was stirred at RT for 6 h. The resin was filtered off and washed with methanol. The solvent of the filtrate was removed by evaporation and the product was purified by reversed phase chromatography (C8) using acetonitrile and aqueous ammonium formate/formic acid solution (0.1 M N4CO2H, 0.1 M HCO2H, pH 4) as eluent. There was obtained 0.23 g (77%) of the title compound. 1H NMR (500 MHz, CD3OD): δ 1.6-2.0 (cm, 6H), 2.6-4.2 (cm, 24H), 7.0-8.0 (cm, 6H), 8.4 (s, 1H); LCMS: m/z 642 (M+1)+.

후처리

  1. filtrationThe resin was filtered off
  2. washwashed with methanol
  3. customThe solvent of the filtrate was removed by evaporation
  4. customthe product was purified by reversed phase chromatography (C8)

출처 및 근거

ORD 기록
ord-1d5c64a5a0634719ab58055bd2f82efe
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08106208B2

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