Cesium carbonate → 5-chloro-8-(4-hydroxypiperidin-1-yl)-N-methoxy-N-methylquinoline-7-carboxamide

HRID 1192531Notes

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.[OH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]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]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[C:7]([N:30]2[CH2:31][CH2:32][CH:27]([OH:26])[CH2:28][CH2:29]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 (0.120 g, 0.301 mmol), 4-hydroxypiperidine (0.0366 g, 0.362 mmol), palladium acetate (1 mg, 0.006 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6 mg, 0.009 mmol), and cesium carbonate (0.14 g, 0.42 mmol) in tetrahydrofuran (6 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and then filtered. The filtrate was washed with brine, dried over sodium sulfate and evaporated to dryness. The resulting residue was purified on silica gel, eluting with 0 to 10% methanol in dichloromethane, to give the desired product (62 mg, 59%). LCMS calculated for C17H21ClN3O3 (M+H)+: m/z=350.1; Found: 350.1.

Workup

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

Sources & evidence

ORD record: ord-b45a882426bf4245bab72442dee74d97
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

Loading…