Dimethyl Sulfoxide → (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-(((S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one

HRID 57495Notes

Reaction equation

HRID 57495 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]=[CH:18][N:17]=[C:16](Cl)[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2].CS(C)=O.Cl.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:34][C:35]([C@@H:38]([NH2:40])[CH3:39])=[CH:36][N:37]=2)=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C>O.CCOC(C)=O.CCCCCCC>[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]=[CH:18][N:17]=[C:16]([NH:40][C@H:38]([C:35]2[S:34][C:33]([C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)=[N:37][CH:36]=2)[CH3:39])[N:15]=1)[CH3:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 90414229HCID 90414229, compoundHCID 90414526(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-chloropyrimidin-4-yl)oxazolidin-2-one

Product 1

HCID 90414586(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-(((S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-oneYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
110 °C

Procedure

To a microwave vial with stir bar was added (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-chloropyrimidin-4-yl)oxazolidin-2-one (147 mg, 0.49 mmol) and DMSO (4 mL). To this reaction mixture was added (S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethanamine HCl (148 mg, 0.54 mmol) and DIEA (0.26 mL, 1.47 mmol). Vial capped and the reaction mixture was heated in a preheated sand bath at 110° C. for 42 hr. The reaction mixture was diluted with water and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2-(((S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (82 mg, 0.16 mmol, 33% yield). 1H NMR (400 MHz, CDCl3) δ 0.82 (br. s., 9H) 0.90-0.98 (m, 3H) 1.71 (d, J=6.90 Hz, 3H) 4.13 (q, J=7.16 Hz, 1H) 4.21-4.32 (m, 1H) 4.42-4.51 (m, 1H) 4.56 (dd, J=8.31, 2.79 Hz, 1H) 5.39 (br. s., 1H) 7.34-7.45 (m, 2H) 7.57 (d, J=5.77 Hz, 1H) 7.64 (s, 1H) 7.76-7.86 (m, 2H) 8.22 (d, J=5.82 Hz, 1H). LCMS m/z 502.3 (M+H)+, Rt 0.92 min.

Workup

  1. customVial capped
  2. extractionextracted with EtOAc
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-118feed73d494734aacf6cf09596c294
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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