Cesium carbonate → HCID 59631367, compound

HRID 1431704Notes

Reaction equation

Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=1.[CH3:16][C@@H:17]1[NH:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.O>[Cl:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=[C:2]([N:22]2[CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][C@@H:17]2[CH3:16])[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 120 °C

Procedure

The 2,4-dichloro-5,7-difluoro-3-methylquinoline (150 mg, 0.60 mmol) was slurried in N-methylpyrrolidinone (1.0 mL) and (S)-tert-butyl 3-methylpiperazine-1-carboxylate (110 mg, 0.54 mmol) and cesium carbonate (360 mg, 1.10 mmol) were added and the reaction mixture was heated at 120° C. for 2.5 h in the microwave. The reaction mixture was then diluted with water (15 mL) and the mixture was extracted with ethyl acetate (3×50 mL). The combined layers were combined and washed with water (1×100 mL) and brine (1×30 mL). The organic layer was dried over magnesium sulfate and the residue was purified by medium pressure chromatography (silica gel, 0 to 15% EtOAc:hexanes) to give (S)-tert-butyl 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-3-methylpiperazine-1-carboxylate. Mass Spectrum (ESI) m/e=412.1 (M+1).

Workup

extractionthe mixture was extracted with ethyl acetate (3×50 mL)
washwashed with water (1×100 mL) and brine (1×30 mL)
dry with materialThe organic layer was dried over magnesium sulfate
customthe residue was purified by medium pressure chromatography (silica gel, 0 to 15% EtOAc:hexanes)

Sources & evidence

ORD record: ord-c877221297464f05a1cb82dd32bc5ba9
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

Loading…