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

HRID 1520523Notes

Reaction equation

HRID 1520523 reaction equation
[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]

Participants

5

Reactant 4

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

Product 1

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

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-7348b61d474d4bcd8e96c26d9906cb21
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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