Water → HCID 90416567, compound

HRID 57509Notes

Reaction equation

HRID 57509 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[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:21]=[CH:20][C:19]=1[C:28]1[CH:29]=[N:30][C:31]([C@@H:34]([NH2:36])[CH3:35])=[N:32][CH:33]=1.CCN(C(C)C)C(C)C.O>CS(C)=O>[F:17][C:18]1[C:23]([C:24]([F:26])([F:25])[F:27])=[CH:22][CH:21]=[CH:20][C:19]=1[C:28]1[CH:33]=[N:32][C:31]([C@@H:34]([NH:36][C:12]2[N:11]=[C:10]([N:5]3[C@@H:4]([C@@H:2]([F:1])[CH3:3])[CH2:8][O:7][C:6]3=[O:9])[CH:15]=[CH:14][N:13]=2)[CH3:35])=[N:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 90415299(R)-4-((S)-1-Fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-oneHCID 90423360(S)-1-(5-(2-fluoro-3-(trifluoromethyl)phenyl)pyrimidin-2-yl)ethanamine

Product 1

HCID 90416567HCID 90416567, compoundYield 76.1%

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) and (S)-1-(5-(2-fluoro-3-(trifluoromethyl)phenyl)pyrimidin-2-yl)ethanamine (75 mg, 0.262 mmol) were taken up in 3 mL DMSO. Hunig's base (57 uL, 0.327 mmol) was added. The mixture was heated to 110 C for 1.5 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, and brine. Combined organics were dried over Na2SO4, filtered and concentrated on silica gel. Column chromatography (25-100% EtOAc/heptane) gave 82 mg white solid. 1H NMR (400 MHz, CDCl3) δ 8.91 (d, J=1.4 Hz, 2H), 8.25 (d, J=5.7 Hz, 1H), 7.79-7.61 (m, 2H), 7.52 (d, J=5.7 Hz, 1H), 7.44 (tt, J=7.7, 0.8 Hz, 1H), 6.12 (s, 1H), 5.32 (s, 1H), 5.08 (br s, 1H), 4.80 (dddd, J=26.5, 9.1, 3.4, 1.5 Hz, 1H), 4.58 (dd, J=8.8, 3.4 Hz, 1H), 4.44 (td, J=9.0, 1.3 Hz, 1H), 1.68 (d, J=8.8 Hz, 3H), 1.43-1.24 (m, 3H). HRMS (A) m/z 495.1611 (M+H)+. Anal. RP-HPLC tR=3.68 min. Purity 96%/100%.

Workup

  1. temperatureThe mixture was heated to 110 C for 1.5 h
  2. extractionextracted with EtOAc (2×30 mL)
  3. washOrganics were washed with 20 mL each water, and brine
  4. dry with materialCombined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on silica gel

Sources & evidence

ORD record
ord-263c2d6403774e849ebc4f0a87fd0155
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

Loading…