Sodium hydride → tert-Butyl{1-[2-(7-fluoro-3-methyl-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 1644422Notes

Reaction equation

HRID 1644422 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:14])[N:7]([CH3:13])[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.[H-].[Na+].CS(O[CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][CH:27]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26][CH2:25]1)(=O)=O.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(OC)C=3)C=CC2=O)CC1)(C)(C)C>C(OCC)(=O)C>[C:34]([O:33][C:31](=[O:32])[NH:30][CH:27]1[CH2:28][CH2:29][N:24]([CH2:23][CH2:22][N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[C:6](=[O:14])[N:7]([CH3:13])[C:8]2=[O:12])[CH2:25][CH2:26]1)([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×HCID 59371209tert-butyl {1-[2-(7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateHCID 667752467-Fluoro-3-methylquinazoline-2,4(1H,3H)-dione2×

Product 1

HCID 86642639tert-Butyl{1-[2-(7-fluoro-3-methyl-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 24%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

7-Fluoro-3-methylquinazoline-2,4(1H,3H)-dione [Intermediate 136] (388 mg, 2.0 mmol) was deprotonated with sodium hydride (100 mg, 60% in oil, 2.4 mmol) and alkylated with 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6) 2.75 mmol) as described for Intermediate 2. Chromatography on silica gel using ethyl acetate in hexanes (10-30%) gave the title compound as a yellow oil (200 mg, 24%).

Sources & evidence

ORD record
ord-75fa527f30804271a258a27104da3e31
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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