Diisopropylethylamine → (S)-4-isopropyl-3-(2-(((S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one

HRID 1850234Notes

Reaction equation

HRID 1850234 reaction equation
Cl[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.[N:17]1[CH:22]=[C:21]([O:23][C:24]2[CH:29]=[CH:28][C:27]([C@@H:30]([NH2:32])[CH3:31])=[CH:26][CH:25]=2)[CH:20]=[N:19][CH:18]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH:13]([C@H:12]1[CH2:11][O:10][C:9](=[O:16])[N:8]1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:32][C@H:30]([C:27]2[CH:26]=[CH:25][C:24]([O:23][C:21]3[CH:20]=[N:19][CH:18]=[N:17][CH:22]=3)=[CH:29][CH:28]=2)[CH3:31])[N:7]=1)([CH3:15])[CH3:14]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 86730167(S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-oneHCID 86730203(S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethanamine

Product 1

HCID 86730288(S)-4-isopropyl-3-(2-(((S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-oneYield 9.9%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

To the solution of (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (43 mg, 0.169 mmol) in NMP (0.7 mL) was added (S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethanamine (41 mg, 0.169 mmol) and DIEA (88 μL, 0.507 mmol). The brown reaction mixture was stirred at 110° C. for 2 days. The reaction mixture was diluted with ethyl acetate and aqueous sodium bicarbonate solution. The separated organic layer was washed with saturated aqueous sodium bicarbonate solution, water and brine. The organic phase was dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography [C-18] to provide (S)-4-isopropyl-3-(2-(((S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (7 mg) as its trifluoroacetic acid salt.

Workup

  1. washThe separated organic layer was washed with saturated aqueous sodium bicarbonate solution, water and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered off
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase column chromatography [C-18]

Sources & evidence

ORD record
ord-15b5b44e3a10433ebe89b9dc13ebf042
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

Loading…