Cesium carbonate → 5-chloro-8-[(3R)-3-hydroxypyrrolidin-1-yl]-N-methoxy-N-methylquinoline-7-carboxamide

HRID 1192497Notes

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]([OH:31])[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>[Cl:17][C:10]1[CH:9]=[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[C:7]([N:26]2[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

Conditions

Temperature: 65 °C

Procedure

A stirred mixture of 5-chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate (0.150 g, 0.376 mmol), (3R)-pyrrolidin-3-ol (0.0394 g, 0.452 mmol, Aldrich), 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, 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 (115 mg, 91%). LCMS calculated for C16H19ClN3O3(M+H)+: m/z=336.1; found: 336.1.

Workup

temperatureThe mixture was cooled
washwashed 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-d314d7f75f8d41838b6795cfc42b7bb4
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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