Diisopropylethylamine → (S)-3-(2-(((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one

HRID 57500Notes

Reaction equation

HRID 57500 reaction equation
[F:1][CH:2]([F:18])[C@@H:3]([C@H:5]1[CH2:9][O:8][C:7](=[O:10])[N:6]1[C:11]1[CH:16]=[CH:15][N:14]=[C:13](F)[N:12]=1)[CH3:4].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:30]=[C:29]([C@@H:31]([NH2:33])[CH3:32])[O:28][N:27]=2)=[CH:22][CH:21]=1.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[N:45]=[C:44]([C@H:46]([NH2:48])[CH3:47])[O:43][N:42]=2)=[CH:37][CH:36]=1.CCN(C(C)C)C(C)C>CS(C)=O.O>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[N:30]=[C:29]([C@@H:31]([NH:33][C:13]3[N:12]=[C:11]([N:6]4[C@@H:5]([C@@H:3]([CH3:4])[CH:2]([F:18])[F:1])[CH2:9][O:8][C:7]4=[O:10])[CH:16]=[CH:15][N:14]=3)[CH3:32])[O:28][N:27]=2)=[CH:24][CH:25]=1.[Cl:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]2[N:45]=[C:44]([C@H:46]([NH:48][C:13]3[N:12]=[C:11]([N:6]4[C@@H:5]([C@@H:3]([CH3:4])[CH:2]([F:18])[F:1])[CH2:9][O:8][C:7]4=[O:10])[CH:16]=[CH:15][N:14]=3)[CH3:47])[O:43][N:42]=2)=[CH:39][CH:40]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 90415701(S)-4-((R)-1,1-difluoropropan-2-yl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-oneHCID 90423917(S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine (R)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine

Product 2

HCID 90414544(S)-3-(2-(((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-oneHCID 90416679(S)-3-(2-(((R)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

A mixture of (S)-4-((R)-1,1-difluoropropan-2-yl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (40 mg, 0.153 mmol), (S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine/(R)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine (mixture of diastereomers ˜3/1, 37.7 mg, 0.168 mmol) and Huenig's base (0.059 mL, 0.337 mmol) in DMSO (0.7 mmol) under argon atmosphere was heated/radiated in the microwave at 140° C. for 15 min. The mixture was diluted with DMSO and water, filtered through a syringe filter and purified by reverse phase HPLC. Selected fractions were collected and lyophilized providing (S)-3-(2-(((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (31.8 mg; first eluted product) and (S)-3-(2-(((R)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (11.5 mg; second eluted product) as their trifluoroacetic acid salts. 410: First eluted product: 1H NMR (500 Mhz, CD3OD) δ ppm 8.22 (s, 1H), 8.03-7.93 (m, 2H), 7.54-7.46 (m, 3H), 5.84 (m, 1H), 5.49 (q, J=7.2 Hz, 1H), 5.13 (dt, J=8.4, 3.1 Hz, 1H), 4.60-4.21 (m, 2H), 2.74 (m, 1H), 1.75 (d, J=7.2 Hz, 3H), 0.90 (br. s, 3H). HRMS m/z 465.1260 (M+H)+; Rt-2.41 min.

Workup

  1. filtrationfiltered through a syringe
  2. filtrationfilter
  3. custompurified by reverse phase HPLC
  4. customSelected fractions were collected

Sources & evidence

ORD record
ord-e39d146efd6d4b1997d1758483c3f1a2
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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