Sodium hydride → tert-Butyl {3-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl}carbamate

HRID 1644373Notes

Reaction equation

HRID 1644373 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.[H-].[Na+].CS(O[CH2:21][CH2:22][N:23]1[CH2:28][CH:27]2[CH:25]([CH:26]2[NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:24]1)(=O)=O.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(OC)C=3)C=CC2=O)CC1)(C)(C)C>ClCCl.CO>[C:33]([O:32][C:30](=[O:31])[NH:29][CH:26]1[CH:27]2[CH:25]1[CH2:24][N:23]([CH2:22][CH2:21][N:7]1[C:6]3[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:5]=3[O:4][CH2:3][C:2]1=[O:1])[CH2:28]2)([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 106548133-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile2×HCID 59371209tert-butyl {1-[2-(7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateHCID 866426262-{6-[(Tert-butoxycarbonyl)amino]-3-azabicyclo[3.1.0]hex-3-yl)ethyl methanesulfonate2×

Product 1

HCID 86642625tert-Butyl {3-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]-3-azabicyclo[3.1.0]hex-6-yl}carbamateYield 94%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile (Intermediate 60) (231 mg, 1.5 mmol) was deprotonated with sodium hydride and alkylated with 2-{6-[(tert-butoxycarbonyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}ethyl methanesulfonate (Intermediate 95) (1.55 mmol) as described for Intermediate 2. Chromatography on silica gel with dichloromethane/methanol (20:1) gave 442 mg (94%) product as a yellow gum.

Sources & evidence

ORD record
ord-161591fa26be4dd7a3e93398ba4a80ba
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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