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

HRID 525591

反応式

HRID 525591 の反応式
[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]

参加物

5

反応物 4

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

生成物 1

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

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-db582ffe85bb4ce2a13313fe90691869
出典データセット
uspto-grants-2016_05
特許番号
US09340564B2

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