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 255254Notes

Reaction equation

HRID 255254 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.COC1C=C2C(C=CC(=O)N2CCN2CCC(NC(=O)OC(C)(C)C)CC2)=CC=1>ClCCl.CO>[C:12]([C:9]1[CH:10]=[CH:11][C:5]2[O:4][CH2:3][C:2](=[O:1])[N:7]([CH2:21][CH2:22][N:23]3[CH2:24][CH:25]4[CH:27]([CH:26]4[NH:29][C:30](=[O:31])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:28]3)[C:6]=2[CH:8]=1)#[N:13]

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-9b51bbe5e2834fff8f2f1ccc03c8561d
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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