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

HRID 1192500Notes

Reaction equation

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]

Participants

Conditions

Temperature: 65 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-76038b1ce3674fa4b1617761a6c38be8
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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