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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 57495
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HRID 57495 반응식
[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]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

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

생성물 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-one수율 33%

시약·촉매·용매 2

HCID 962Water용매HCID 21899848Ethylacetate heptane용매

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온도
110 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-118feed73d494734aacf6cf09596c294
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09434719B2

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