Morpholine → 2,2-Difluoro-1-((4S,5R)-4-fluoromethyl-2,2-dimethyl-5-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-oxazolidin-3-yl)-ethanone

HRID 1520504Notes

Reaction equation

HRID 1520504 reaction equation
[F:1][CH:2]([F:33])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([CH:24](OS(C)(=O)=O)[CH3:25])=[N:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:32])[CH3:31])=[O:4].C(N(C(C)C)CC)(C)C.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(#N)C>[F:33][CH:2]([F:1])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[N:22][C:21]([CH:24]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)[CH3:25])=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)[O:7][C:6]1([CH3:32])[CH3:31])=[O:4]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 86695453Methanesulfonic acid 1-(5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-yl)-ethyl ester

Product 1

HCID 866954552,2-Difluoro-1-((4S,5R)-4-fluoromethyl-2,2-dimethyl-5-{4-[6-(1-morpholin-4-yl-ethyl)-pyridin-3-yl]-phenyl}-oxazolidin-3-yl)-ethanoneYield 68.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of Methanesulfonic acid 1-(5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-yl)-ethyl ester (0.150 g, 0.309 mmol) in acetonitrile (2 mL) is added diisopropylethylamine (0.161 mL, 0.926 mmol) and morphline (0.054 mL, 0.617 mmol). Reaction mixture is stirred at 60° C. for 16 h. The solvent is evaporated in vacuo and the crude material is purified by combiflash using 1% methanol:CH2Cl2 as an eluent to afford the title compound (0.101 g). 1H NMR (400 MHz, CDCl3) δ 1.33 (d, J=6.48 Hz, 3H), 1.53 (s, 3H), 1.60 (s, 3H), 2.32-2.33 (m, 2H), 2.45-2.50 (m, 2H), 3.53-3.58 (m, 4H), 3.60-3.63 (m, 1H), 4.54-4.58 (m, 0.5H), 4.66-4.72 (m, 1H), 4.80-4.84 (m, 0.5H), 4.90-4.94 (m, 1H) 5.26 (d, J=4 Hz, 1H), 6.64 (t, J=52.32, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.59 (d, J=8.12 Hz, 2H), 7.78 (d, J=8.24 Hz, 2H), 8.06-8.10 (dd, J1=8.8 Hz, J2=6.48 Hz, 1H), 8.83 (d, J=2.24 Hz, 1H). LCMS-not ionized.

Workup

  1. customReaction mixture
  2. customThe solvent is evaporated in vacuo
  3. customthe crude material is purified by combiflash

Sources & evidence

ORD record
ord-46ae97d15811443eb3822d953444b6f0
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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