Cesium carbonate → 8-[(3S)-3-(acetylamino)pyrrolidin-1-yl]-5-chloro-N-methoxy-N-methylquinoline-7-carboxamide

HRID 1192500Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1192500
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.[NH:26]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:34])[CH3:33])[CH2:27]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>[C:32]([NH:31][C@H:28]1[CH2:29][CH2:30][N:26]([C:7]2[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])=[CH:9][C:10]([Cl:17])=[C:11]3[C:16]=2[N:15]=[CH:14][CH:13]=[CH:12]3)[CH2:27]1)(=[O:34])[CH3:33]

Komponenten

8

Edukt 3

HCID 10796Cesium carbonateHCID 7021471(S)-(-)-3-AcetamidopyrrolidineHCID 866561725-Chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate

Produkt 1

HCID 866561778-[(3S)-3-(acetylamino)pyrrolidin-1-yl]-5-chloro-N-methoxy-N-methylquinoline-7-carboxamideAusbeute 66,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 634876Binap, (A+-)-KatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A stirred mixture of 5-chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate (0.120 g, 0.301 mmol), N-[(3S)-pyrrolidin-3-yl]acetamide (0.0464 g, 0.362 mmol, Lancaster), palladium acetate (1 mg, 0.006 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6 mg, 0.009 mmol), and cesium carbonate (0.274 g, 0.843 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 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 (75 mg, 66%). LCMS calculated for C18H22ClN4O3(M+H)+: m/z=377.1; found: 377.1.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-76038b1ce3674fa4b1617761a6c38be8
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680108B2

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