Diisopropylethylamine → (R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-one

HRID 57473Notes

Reaction equation

HRID 57473 reaction equation
[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[C:18]([CH:20]([F:22])[F:21])[N:17]=[C:16](S(C)(=O)=O)[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:38]=[C:37]([C@@H:39]([NH2:41])[CH3:40])[O:36][N:35]=2)=[CH:30][CH:29]=1.C(N(C(C)C)C(C)C)C>CS(C)=O.C(Cl)Cl.O>[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[C:18]([CH:20]([F:22])[F:21])[N:17]=[C:16]([NH:41][C@H:39]([C:37]2[O:36][N:35]=[C:34]([C:31]3[CH:32]=[CH:33][C:28]([Cl:27])=[CH:29][CH:30]=3)[N:38]=2)[CH3:40])[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 40800146(1S)-1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethan-1-amineHCID 90417088(R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylsulfonyl)pyrimidin-4-yl)oxazolidin-2-one

Product 1

HCID 90414149(R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-oneYield 37%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylsulfonyl)pyrimidin-4-yl)oxazolidin-2-one (0.146 g, 0.371 mmol), (S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethanamine (91 mg, 0.41 mmol, 1.1 equiv), and N-ethyl-N-isopropylpropan-2-amine (0.097 mL, 0.56 mmol, 1.5 equiv) in DMSO (2.0 mL) was heated at 85° C. for 18 h. The reaction was cooled to room temperature and diluted with DCM (20 mL) and water (20 mL). The layers were separated and the aqueous layer was extracted with DCM (20 mL). The combined organic layers were washed with saturated aqueous NaCl (10 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 20% to 60%) provided (R)-4-((R)-1-tert-butoxyethyl)-3-(2-((S)-1-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)ethylamino)-6-(difluoromethyl)pyrimidin-4-yl)oxazolidin-2-one as a yellow oily solid in 37% yield. MS m/z 537.2 (M+H)+; Rt-1.22 min.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM (20 mL)
  3. washThe combined organic layers were washed with saturated aqueous NaCl (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9a8f5f89df9145229cd62d9401a20eea
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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