Diisopropylethylamine → 2,2-Difluoro-1-[(4S,5R)-4-fluoromethyl-5-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2,2-dimethyl-oxazolidin-3-yl]-ethanone

HRID 1520473Notes

Reaction equation

HRID 1520473 reaction equation
Cl.[F:2][CH2:3][CH2:4][CH2:5][NH2:6].C(N(C(C)C)CC)(C)C.[F:16][CH:17]([F:47])[C:18]([N:20]1[C@H:24]([CH2:25][F:26])[C@@H:23]([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:34]=[CH:35][C:36]([CH2:39]OS(C)(=O)=O)=[N:37][CH:38]=3)=[CH:29][CH:28]=2)[O:22][C:21]1([CH3:46])[CH3:45])=[O:19]>C(#N)C>[F:47][CH:17]([F:16])[C:18]([N:20]1[C@H:24]([CH2:25][F:26])[C@@H:23]([C:27]2[CH:28]=[CH:29][C:30]([C:33]3[CH:38]=[N:37][C:36]([CH2:39][NH:6][CH2:5][CH2:4][CH2:3][F:2])=[CH:35][CH:34]=3)=[CH:31][CH:32]=2)[O:22][C:21]1([CH3:45])[CH3:46])=[O:19]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 219074553-Fluoropropan-1-amine hydrochlorideHCID 86695429Methanesulfonic acid 5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-ylmethyl ester

Product 1

HCID 866954312,2-Difluoro-1-[(4S,5R)-4-fluoromethyl-5-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2,2-dimethyl-oxazolidin-3-yl]-ethanoneYield 97.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-Fluoro-propylamine hydrochloride (0.072 g, 0.636 mmol) in acetonitrile (5 mL) is added diisopropylethylamine (0.082 mL, 0.636 mmol) at room temperature. After stirring for 30 minutes methane sulfonic acid 5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-ylmethyl ester (0.1 g, 0.211 mmol) is added then the resulting mixture is stirred at room temperature for overnight. Solvent is evaporated under reduced pressure and the crude material is purified by combi-flash chromatography using 12% methanol in CH2Cl2 as an eluent to afford the title compound (0.093 g). 1H-NMR (400 MHz, DMSO-d6) δ: 1.52 (s, 3H), 1.60 (S, 3H), 2.06-2.14 (m, 2H), 3.57-3.60 (m, 2H), 4.35 (s, 2H), 4.49-4.51 (m, 1H), 4.52-4.56 (m, 0.5H), 4.57-4.63 (m, 1H), 4.64-4.70 (m, 1H), 4.83-4.86 (m, 0.5H), 4.93-4.97 (m, 1H), 5.28 (d, J=3.48 Hz, 1H), 6.66 (t, J=52.3 Hz, 1H), 7.61-7.65 (m, 3H), 7.84 (d, J=8.2 Hz, 2H), 8.21-8.23 (dd, J1=3.04 Hz, J2=8.16 Hz, 1H), 8.97 (d, J=1.96 Hz, 1H). LC-MS (m/z): [M+H]=454.1.

Workup

  1. additionis added
  2. customSolvent is evaporated under reduced pressure
  3. customthe crude material is purified by combi-flash chromatography

Sources & evidence

ORD record
ord-7662096384ba402fb7f79005866f4429
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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