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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Cesium carbonate → (R)-3-(5-fluoro-2-(((S)-1-(1-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)piperidin-4-yl)ethyl)amino)pyrimidin-4-yl)-4-((S)-1-hydroxyethyl)oxazolidin-2-one

HRID 57487
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HRID 57487 반응식
C([O:5][C@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[C:19]([F:20])=[CH:18][N:17]=[C:16]([NH:21][C@H:22]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH3:23])[N:15]=1)[CH3:7])(C)(C)C.Br[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([C:37]([CH3:43])([CH3:42])[C:38]([F:41])([F:40])[F:39])[CH:32]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:20][C:19]1[C:14]([N:9]2[C@@H:8]([C@@H:6]([OH:5])[CH3:7])[CH2:12][O:11][C:10]2=[O:13])=[N:15][C:16]([NH:21][C@H:22]([CH:24]2[CH2:25][CH2:26][N:27]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]([C:37]([CH3:43])([CH3:42])[C:38]([F:41])([F:40])[F:39])[CH:32]=3)[CH2:28][CH2:29]2)[CH3:23])=[N:17][CH:18]=1
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 716828104-Bromo-2-(2,2,2-trifluoro-1,1-dimethylethyl)pyridineHCID 90417340(R)-4-((S)-1-(tert-butoxy)ethyl)-3-(5-fluoro-2-(((S)-1-(piperidin-4-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one

생성물 1

HCID 90415196
(R)-3-(5-fluoro-2-(((S)-1-(1-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)piperidin-4-yl)ethyl)amino)pyrimidin-4-yl)-4-((S)-1-hydroxyethyl)oxazolidin-2-one
수율 18.1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

실험 절차

A cloudy solution of (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(5-fluoro-2-(((S)-1-(piperidin-4-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (21 mg, 0.051 mmol), 4-bromo-2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine (14 mg, 0.051 mmol), Pd(OAc)2 (1 mg, 5 umol), BINAP (3 mg, 5 umol), and Cs2CO3 (25 mg, 0.077 mmol) in 6 mL toluene was heated at 90° C. overnight. The mixture was cooled to room temperature, and filtered through Celite. The celite cake was rinsed with 5 mL EtOAc. The filtrate was poured into 5 mL water. Organic layer was separated, and the aqueous was further extracted with EtOAc (5 mL). The organic extracts were combined and concentrated by rotary evaporation. The resulting crude was dissolved in DCM (1 mL), TFA (1 mL) was added. The reaction solution was stirred for 2 hour at room temperature and was concentrated by rotary evaporation. The resulting residue was dissolved in DCM (2 mL) and water (2 mL) and the pH was adjusted to ˜9 with NH4OH. The DCM layer was separated and concentrated by rotary evaporation. The crude was dissolved in a mixture of MeOH (1 mL) and DMSO (1 mL) and purified by reverse phase HPLC. Selected fractions were collected and concentrated by rotary evaporation to afford the title product as a colorless oil (5 mg) (ratio of two peaks with same MS: 93/7% by LC-MS). (400 MHz, CD2Cl2) δ 8.16-8.08 (m, 2H), 6.79-6.75 (m, 1H), 6.57-6.52 (m, 1H), 4.97-4.86 (m, 1H), 4.47-4.39 (m, 2H), 4.33-4.25 (m, 1H), 4.11-4.02 (m, 1H), 3.89-3.75 (m, 3H), 2.97 (br s, 1H), 2.80-2.67 (m, 2H), 1.84-1.67 (m, 2H), 1.67-1.55 (m, 1H), 1.48 (s, 6H), 1.38-1.15 (m, 2H), 1.11 (d, J=5.91 Hz, 3H), 1.07 (d, J=5.91 Hz, 3H), HRMS(C) tR=3.59 min; MS m/z 541.2557 (M+H)+

후처리

  1. filtrationfiltered through Celite
  2. washThe celite cake was rinsed with 5 mL EtOAc
  3. additionThe filtrate was poured into 5 mL water
  4. customOrganic layer was separated
  5. extractionthe aqueous was further extracted with EtOAc (5 mL)
  6. concentrationconcentrated by rotary evaporation
  7. dissolutionThe resulting crude was dissolved in DCM (1 mL)
  8. additionTFA (1 mL) was added
  9. concentrationwas concentrated by rotary evaporation
  10. dissolutionThe resulting residue was dissolved in DCM (2 mL)
  11. customThe DCM layer was separated
  12. concentrationconcentrated by rotary evaporation
  13. dissolutionThe crude was dissolved in a mixture of MeOH (1 mL) and DMSO (1 mL)
  14. custompurified by reverse phase HPLC
  15. customSelected fractions were collected
  16. concentrationconcentrated by rotary evaporation

출처 및 근거

ORD 기록
ord-1ba8345eefa6411089b5f27a9156a4a9
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09434719B2

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