Cesium acetate → HCID 178485471, 화합물

HRID 707307노트

반응식

HRID 707307 반응식
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[C:14]([CH3:22])([CH3:21])[C:13]2=[O:23])[CH2:9]1)(C)(C)C.C([O-])(=O)C.[Cs+].BrC1[CH:40]=[CH:39][C:34]([C:35]([NH:37][CH3:38])=[O:36])=[CH:33][N:32]=1>[Cu]>[CH3:22][C:14]1([CH3:21])[C:15]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[N:12]([C@H:10]2[CH2:11][C@H:8]([NH:7][C:6]3[CH:40]=[CH:39][C:34]([C:35]([NH:37][CH3:38])=[O:36])=[CH:33][N:32]=3)[CH2:9]2)[C:13]1=[O:23]

참가 물질

5

반응물 3

HCID 5152919Cesium acetateHCID 230921426-Bromo-N-methylnicotinamideHCID 178454100HCID 178454100, 화합물

생성물 1

HCID 178485471HCID 178485471, 화합물수율 36.7%

시약·촉매·용매 1

HCID 23978Copper촉매

반응 조건

온도
100 °C

실험 절차

Intermediate 26 (100 mg, 0.373 mmol), cesium acetate (516 mg, 2.69 mmol), 6-bromo-n-methylnicotinamide (120 mg, 0.560 mmol), and copper (1.899 mg, 0.030 mmol) were weighed into a microwave vial. The vial was evacuated and flushed with nitrogen. DMSO (467 μl) was then added and the mixture was heated at 100° C. for 20 h. The mixture was diluted with ethyl acetate and washed with aqueous ammonium hydroxide. The aqueous layer was back extracted with ethyl acetate and the combined organics dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by silica chromatography, eluting with a gradient of hexane/ethyl acetate (50-100%) to provide 6-((trans-3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)cyclobutyl)amino)-N-methylnicotinamide (50 mg, 0.137 mmol, 36.6% yield) as off-white solid. M+1: 366. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 6 H) 2.28-2.40 (m, 2 H) 3.00 (d, J=4.82 Hz, 3 H) 3.39-3.54 (m, 2 H) 4.50 (br. s., 1 H) 5.28 (quin, J=8.59 Hz, 1 H) 5.38 (br. d, J=4.80 Hz, 1 H) 5.98 (br. s., 1 H) 6.34 (d, J=8.77 Hz, 1 H) 6.96 (dd, J=7.31, 5.26 Hz, 1 H) 7.43 (dd, J=7.16, 1.61 Hz, 1 H) 7.91 (dd, J=8.70, 2.41 Hz, 1 H) 8.18 (dd, J=5.26, 1.61 Hz, 1 H) 8.51 (d, J=2.05 Hz, 1 H)

후처리

  1. customThe vial was evacuated
  2. customflushed with nitrogen
  3. additionDMSO (467 μl) was then added
  4. additionThe mixture was diluted with ethyl acetate
  5. washwashed with aqueous ammonium hydroxide
  6. extractionThe aqueous layer was back extracted with ethyl acetate
  7. dry with materialthe combined organics dried with magnesium sulfate
  8. customevaporated to dryness under reduced pressure
  9. customThe crude product was purified by silica chromatography
  10. washeluting with a gradient of hexane/ethyl acetate (50-100%)

출처 및 근거

ORD 기록
ord-9061781579084011ba3d970192ff2b49
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174992B2

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