Water → (S)-3-(2-(1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethylamino) pyrimidin-4-yl)-4-isopropyloxazolidin-2-one

HRID 1850214Notes

Reaction equation

HRID 1850214 reaction equation
F[C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[CH:4][N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:25]=[N:26][C:27]([CH:30]([NH2:32])[CH3:31])=[N:28][CH:29]=2)=[CH:20][C:19]=1[CH3:33].C(N(C(C)C)CC)(C)C.O>CS(C)=O>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[N:28][C:27]([CH:30]([NH:32][C:2]3[N:7]=[C:6]([N:8]4[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]4=[O:16])[CH:5]=[CH:4][N:3]=3)[CH3:31])=[N:26][CH:25]=2)=[CH:20][C:19]=1[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 86730137HCID 86730137, compoundHCID 867302681-(5-(4-Fluoro-3-methylphenyl)pyrimidin-2-yl)ethanamine

Product 1

HCID 86730267(S)-3-(2-(1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethylamino) pyrimidin-4-yl)-4-isopropyloxazolidin-2-oneYield 27.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (S)-3-(2-fluoropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (1055 mg, 4.68 mmol), 1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethanamine (1300 mg, 5.62 mmol, 1.2 equiv) and diisopropylethylamine (908 mg, 7.03 mmol, 1.5 equiv) in DMSO (20 mL) was heated at 110° C. for 1 h. The reaction mixture was poured into water (60 mL) and extracted with EtOAc (2×50 mL). Combined organics were washed with water (40 mL), brine (40 mL), dried over Na2SO4, filtered and concentrated directly onto silica gel. Silica gel chromatography provided the mixed distereomers of (S)-3-(2-(1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethylamino) pyrimidin-4-yl)-4-isopropyloxazolidin-2-one (560 mg). Chiral separation was carried out with SFC (ID, 5 μm, 20×250 mm) using 35% MeOH in CO2 to give (S)-3-(2-((S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one and (S)-3-(2-((R)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one.

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. washCombined organics were washed with water (40 mL), brine (40 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated directly onto silica gel

Sources & evidence

ORD record
ord-d1858f7ed8c34d9eaa98b5a09646c5f4
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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