Sodium hydride → tert-butyl {1-[2-(7-bromo-5-fluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 1644466Notes

Reaction equation

HRID 1644466 reaction equation
BrC1C=C(F)C=C2C=1C=CC(=O)N2.[Br:14][C:15]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21](=[O:25])[NH:22]2)=[C:17]([F:26])[CH:16]=1.[H-].[Na+].CS(O[CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH:39]([NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38][CH2:37]1)(=O)=O.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(F)C=3)N=CC2=O)CC1)(C)(C)C>C(OCC)(=O)C>[C:46]([O:45][C:43](=[O:44])[NH:42][CH:39]1[CH2:40][CH2:41][N:36]([CH2:35][CH2:34][N:22]2[C:23]3[C:18](=[C:17]([F:26])[CH:16]=[C:15]([Br:14])[CH:24]=3)[CH:19]=[CH:20][C:21]2=[O:25])[CH2:37][CH2:38]1)([CH3:49])([CH3:48])[CH3:47]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×HCID 59397942tert-butyl{1-[2-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateHCID 667743297-bromo-5-fluoroquinolin-2(1H)-one2×HCID 667743565-bromo-7-fluoroquinolin-2(1H)-one

Product 1

HCID 86642655tert-butyl {1-[2-(7-bromo-5-fluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 33%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-7-fluoroquinolin-2(1H)-one and 7-bromo-5-fluoroquinolin-2(1H)-one (Intermediate 177 and 178, 3.0 g, 9.4 mmol) was reacted with sodium hydride (60% in oil, 0.20 g, 5.0 mmol) and 2-{4-[tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6, 9.4 mmol) as described for Intermediate 141. Chromatography on silica gel with a gradient of 50-75% ethyl acetate in hexanes gave 0.63 g (33%) of the regioisomeric product mixture, which was carried on without further purification to the next step.

Sources & evidence

ORD record
ord-451423c136324b4c9fe11f51caa2604d
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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