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Cesium carbonate → 5-chloro-N-methoxy-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-N-methylquinoline-7-carboxamide

HRID 1192503
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HRID 1192503 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[CH3:26][O:27][CH2:28][C@H:29]1[CH2:33][CH2:32][CH2:31][NH:30]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:17][C:10]1[CH:9]=[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[C:7]([N:30]2[CH2:31][CH2:32][CH2:33][C@@H:29]2[CH2:28][O:27][CH3:26])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2
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참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 866561725-Chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate

생성물 1

HCID 866561785-chloro-N-methoxy-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-N-methylquinoline-7-carboxamide수율 96.5%

시약·촉매·용매 4

HCID 167845
palladium(II) acetate
촉매
HCID 634876Binap, (A+-)-촉매
HCID 6344Dichloromethane용매
HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

A stirred mixture of 5-chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate (0.150 g, 0.376 mmol), (2R)-2-(methoxymethyl)pyrrolidine (0.0521 g, 0.452 mmol, Fluka), palladium acetate (2 mg, 0.008 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (7 mg, 0.01 mmol), and cesium carbonate (0.343 g, 1.05 mmol) in tetrahydrofuran (4 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane, and filtered. The filtrate was washed with brine, dried over sodium sulfate, and evaporated to dryness. The resultant residue was purified on silica gel, eluting with 0 to 10% MeOH in dichloromethane, to give the desired product (132 mg, 96%). LCMS calculated for C18H23ClN3O3(M+H)+: m/z=364.1; found: 364.1.

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe resultant residue was purified on silica gel
  7. washeluting with 0 to 10% MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-412605aaf6f8497da8a425fc0fb33c2d
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08680108B2

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