Water → (R)-3-(2-(((S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethyl)amino)pyrimidin-4-yl)-4-((S)-1-fluoroethyl)oxazolidin-2-one

HRID 57511Notes

Reaction equation

HRID 57511 reaction equation
[F:1][C@H:2]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]=[C:12](F)[N:11]=1)[CH3:3].[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:25]=[N:26][C:27]([C@@H:30]([NH2:32])[CH3:31])=[N:28][CH:29]=2)=[CH:20][C:19]=1[CH3:33].CCN(C(C)C)C(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]([C@@H:30]([NH:32][C:12]3[N:11]=[C:10]([N:5]4[C@@H:4]([C@@H:2]([F:1])[CH3:3])[CH2:8][O:7][C:6]4=[O:9])[CH:15]=[CH:14][N:13]=3)[CH3:31])=[N:26][CH:25]=2)=[CH:20][C:19]=1[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 90415299(R)-4-((S)-1-Fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-oneHCID 90423133(S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethanamine

Product 1

HCID 90416226(R)-3-(2-(((S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethyl)amino)pyrimidin-4-yl)-4-((S)-1-fluoroethyl)oxazolidin-2-oneYield 95.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(R)-4-((S)-1-fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (50 mg, 0.218 mmol), (S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethanamine (60.5 mg, 0.262 mmol), and DIPEA (57 ul, 0.327 mmol) were taken up in 3 mL DMSO. Heated to 110 C for 1 h. The reaction mixture was poured into 30 mL water and extracted with EtOAc (2×30 mL). Organics were washed with 20 mL each water, brine, and dried over Na2SO4, and filtered and concentrated on silica gel. Column chromatography (25-100% EtOAc/hept) gave the desired product (92 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 2H), 8.25 (d, J=5.7 Hz, 1H), 7.51 (d, J=5.7 Hz, 1H), 7.42-7.31 (m, 2H), 7.21-7.12 (m, 1H), 6.15 (s, 1H), 5.28 (s, 2H), 4.80 (dddd, J=26.6, 9.0, 3.5, 1.6 Hz, 1H), 4.57 (dd, J=8.8, 3.4 Hz, 1H), 4.44 (td, J=9.0, 1.3 Hz, 1H), 2.39 (d, J=1.9 Hz, 3H), 1.66 (d, J=6.9 Hz, 3H), 1.35-1.24 (m, 3H). HRMS (A) m/z 441.1849 (M+H)+. Anal. RP-HPLC tR=3.10 min. Purity 100%/100%.

Workup

  1. temperatureHeated to 110 C for 1 h
  2. extractionextracted with EtOAc (2×30 mL)
  3. washOrganics were washed with 20 mL each water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on silica gel

Sources & evidence

ORD record
ord-96412ed6120c471080e3ff1c48f5d3a7
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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