Methanol → 2,2-Dichloro-N-{(1S,2R)-2-[4-(6-dimethylamino-methyl-pyridin-3-yl)-phenyl]-1-fluoromethyl-2-hydroxy-ethyl}-acetamide

HRID 1520523노트

반응식

HRID 1520523 반응식
[NH2:1][C@H:2]([CH2:21][F:22])[C@H:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[N:13][C:14](CN(C)C)=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)[OH:4].[Cl:23][CH:24]([Cl:30])[C:25](OCC)=[O:26].[CH2:31]([N:33](CC)[CH2:34]C)C.[CH3:38]O>>[Cl:23][CH:24]([Cl:30])[C:25]([NH:1][C@H:2]([CH2:21][F:22])[C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:12]([CH3:38])=[N:13][C:14]([N:33]([CH3:34])[CH3:31])=[CH:15][CH:16]=2)=[CH:9][CH:10]=1)[OH:4])=[O:26]

참가 물질

5

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 10808Ethyl dichloroacetateHCID 86695472(1S,2S)-2-Amino-1-[4-(6-dimethylaminomethyl-pyridin-3-yl)-phenyl]-3-fluoro-propan-1-ol

생성물 1

HCID 866954732,2-Dichloro-N-{(1S,2R)-2-[4-(6-dimethylamino-methyl-pyridin-3-yl)-phenyl]-1-fluoromethyl-2-hydroxy-ethyl}-acetamide

실험 절차

To a stirred solution of (1S,2S)-2-Amino-1-[4-(6-dimethylaminomethyl-pyridin-3-yl)-phenyl]-3-fluoro-propan-1-ol (60 mg, 0.143 mmol) in dry methanol (0.26 mL) is added ethyl dichloroacetate (45 mg, 0.287 mmol) and triethylamine (29 mg, 0.287 mmol) at room temperature and reaction mixture stirred for 24 hours. Solvent is evaporated in vacuo and the crude material purified by column chromatography eluting in 6% methanol in CH2Cl2 to afford title compound (13 mg): 1H-NMR (400 MHz, DMSO-d6) δ: 2.20 (s, 6H), 3.54 (s, 2H), 4.17-4.24 (m, 1H), 4.27-4.31 (m, 0.5H), 4.39-4.41 (m, 0.5H), 4.56-4.58 (m, 0.5H), 4.59-4.71 (m, 0.5H), 4.89 (m, 1H), 4.99 (d, 1H, J=4 Hz), 6.52 (s, 1H), 7.45-7.49 (m, 3H), 7.68 (d, 2H, J=8.24 Hz), 8.03 (dd, 1H, J1=8.08 Hz, J2=2.4 Hz), 8.64 (d, 1H, J=8.8 Hz), 8.77 (d, 1H, J=2.04 Hz). LC-MS (m/z): [M+H]=414.

후처리

  1. customreaction mixture
  2. customSolvent is evaporated in vacuo
  3. customthe crude material purified by column chromatography
  4. washeluting in 6% methanol in CH2Cl2

출처 및 근거

ORD 기록
ord-7348b61d474d4bcd8e96c26d9906cb21
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073894B2

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