Water → (1R,2R,6S)-2-(tert-butyldimethylsilyloxy)-6-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-2-methylcyclohexanol

HRID 527011

반응식

HRID 527011 반응식
[NH2:1][C@@H:2]1[C@@H:7]([OH:8])[C@@:6]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])([CH3:9])[CH2:5][CH2:4][CH2:3]1.[Cl:18][C:19]1[CH:20]=[C:21]2[C:27]([C:28]3[N:33]=[C:32](S(C)=O)[C:31]([F:37])=[CH:30][N:29]=3)=[CH:26][N:25]([S:38]([C:41]3[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=3)(=[O:40])=[O:39])[C:22]2=[N:23][CH:24]=1.C(N(C(C)C)C(C)C)C.O>C1COCC1>[Si:11]([O:10][C@:6]1([CH3:9])[CH2:5][CH2:4][CH2:3][C@H:2]([NH:1][C:30]2[C:31]([F:37])=[CH:32][N:33]=[C:28]([C:27]3[C:21]4[C:22](=[N:23][CH:24]=[C:19]([Cl:18])[CH:20]=4)[N:25]([S:38]([C:41]4[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=4)(=[O:40])=[O:39])[CH:26]=3)[N:29]=2)[C@H:7]1[OH:8])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

참가 물질

6

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridineHCID 68007680(1R,2R,6S)-6-amino-2-[tert-butyl(dimethyl)silyl]oxy-2-methyl-cyclohexanol2회

생성물 1

HCID 68007206(1R,2R,6S)-2-(tert-butyldimethylsilyloxy)-6-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-2-methylcyclohexanol

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
70 °C

실험 절차

To a stirred suspension of (1R,2R,6S)-6-amino-2-[tert-butyl(dimethyl)silyl]oxy-2-methyl-cyclohexanol, 50e, (0.16 g, 0.62 mmol) in THF (8 mL) in a microwave sealed tube vessel was added 5-chloro-3-(5-fluoro-4-(methylsulfinyl)pyrimidin-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 1a, (0.29 g, 0.63 mmol) followed by N-ethyl-N-isopropyl-propan-2-amine (0.13 mL, 0.74 mmol). The resulting reaction mixture was capped and warmed to 70° C., stirred for 14 h. The reaction mixture was cooled to ambient temperature, added water (2 mL), concentrated under reduced pressure to remove THF. The crude product was diluted with ethyl acetate (25 mL), insoluble material (sulfone 1a) was removed by filtration. The organic layer was separated, washed with brine (2×5 mL), dried over Na2SO4, filter and concentrated under reduced pressure. The crude product was purified by silica-gel plug using 10-30% ethyl acetate in hexanes as eluant to afford 350 mg of (1R,2R,6S)-2-[tert-butyl(dimethyl)silyl]oxy-6-[[2-methyl[5-chloro-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyridin-4-yl]amino]cyclohexanol (50f).

후처리

  1. customsealed tube vessel
  2. customThe resulting reaction mixture
  3. customwas capped
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. customto remove THF
  7. additionThe crude product was diluted with ethyl acetate (25 mL), insoluble material (sulfone 1a)
  8. customwas removed by filtration
  9. customThe organic layer was separated
  10. washwashed with brine (2×5 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was purified by silica-gel plug

출처 및 근거

ORD 기록
ord-12236015b93f4293a1c0fe5bf6cb806c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

연결된 노트

불러오는 중…