Cesium carbonate → 1-[5-Chloro-8-(3-methoxypyrrolidin-1-yl)quinolin-7-yl]ethanone

HRID 1192617노트

반응식

HRID 1192617 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[CH3:24][O:25][CH:26]1[CH2:30][CH2:29][NH:28][CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:28]2[CH2:29][CH2:30][CH:26]([O:25][CH3:24])[CH2:27]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 220176303-Methoxypyrrolidine hydrochlorideHCID 58368658HCID 58368658, 화합물

생성물 1

HCID 583684161-[5-Chloro-8-(3-methoxypyrrolidin-1-yl)quinolin-7-yl]ethanone수율 43%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 634876Binap, (A+-)-촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), 3-methoxypyrrolidine hydrochloride (0.056 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.33 g, 1.0 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and evaporated under reduced pressure. The residue was purified on silica gel (eluting with 0 to 10% methanol in dichloromethane) to give the desired product (44.5 mg, 43%). LCMS calculated for C16H18ClN2O2 (M+H)+: m/z=305.1; Found: 305.1.

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe residue was purified on silica gel (eluting with 0 to 10% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-55fd99a48da6415c8d3d0f066ed31082
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680108B2

반응 노트

불러오는 중…