Acetonitrile → HCID 86730216, compound

HRID 1850213Notes

Reaction equation

HRID 1850213 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.[F:17][C:18]([F:28])([F:27])[CH:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[NH2:20].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CC#N>CCCCO>[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:20][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:18]([F:17])([F:27])[F:28])[N:7]=1)([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 89166alpha-(Trifluoromethyl)benzenemethanamineHCID 521998p-Toluenesulfonic acid monohydrate2×HCID 86730167(S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one

Product 1

HCID 86730216HCID 86730216, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (163 mg, 0.674 mmol), 2,2,2-trifluoro-1-phenylethanamine (624 mg, 3.56 mmol, 5.3 equiv) and p-toluenesulfonic acid monohydrate (321 mg, 1.69 mmol, 2.5 equiv) in n-BuOH (3 mL) was heated at 110° C. for 2 h and treated with additional p-toluenesulfonic acid monohydrate (321 mg, 1.69 mmol, 2.5 equiv), then heated at 110° C. for 1½ h. After cooling, the solid reaction mixture was treated with MeCN, sonicated and filtered. The filtrated was concentrated and purified by silica gel column chromatography (EtOAc/Heptane 0 to 30%) to give (4S)-4-isopropyl-3-(2-(2,2,2-trifluoro-1-phenylethylamino)pyrimidin-4-yl)oxazolidin-2-one (65 mg) in 25% yield. HRMS(B) m/z 381.1545 (M+H)+. Anal. RP-HPLC tR=4.31//4.46 min (1.0 mL/min flow rate with gradient from 5% to 15% acetonitrile with 0.05% formic acid in 5.00 min and then 15% to 95% acetonitrile with 0.05% formic acid from 5.00 min to 9.50 min, aqueous phase modified with 0.1% formic acid. Silica gel column chromatography separated the two diastereomers (S)-4-isopropyl-3-(2-((R)-2,2,2-trifluoro-1-phenylethylamino)pyrimidin-4-yl)oxazolidin-2-one and (S)-4-isopropyl-3-(2-((S)-2,2,2-trifluoro-1-phenylethylamino)pyrimidin-4-yl)oxazolidin-2-one.

Workup

  1. temperatureAfter cooling
  2. customthe solid reaction mixture
  3. customsonicated
  4. filtrationfiltered
  5. concentrationThe filtrated was concentrated
  6. custompurified by silica gel column chromatography (EtOAc/Heptane 0 to 30%)

Sources & evidence

ORD record
ord-65f0920229a1437b8fd1fe6c53fccb33
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

Loading…