Trimethyl orthoformate → 6-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)quinazolin-4(3H)-one

HRID 77407Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][C@@H:15]3[CH2:17][C@H:12]2[CH2:13][N:14]3[CH3:18])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH:19](OC)(OC)OC.C([O-])(=O)C.[NH4+]>CO>[CH3:18][N:14]1[CH2:13][C@@H:12]2[CH2:17][C@H:15]1[CH2:16][N:11]2[C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[CH:19][NH:6][C:4]2=[O:5]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution 2-amino-5-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)benzamide (Intermediate 31D) (1 g, 3.83 mmol) in methanol (15 ml) was added trimethyl orthoformate (812 mg, 7.66 mmol) and ammonium acetate (0.60 g, 7.66 mmol). The vessel was sealed and the reaction heated at 120° C. for 4 hours. The methanol was then removed and the product chromatographed on silica elueting with 5% methanol in dichloromethane to afford 6-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)quinazolin-4(3H)-one (0.60 g, 2.33 mmol) as an off-white solid.

Workup

customThe vessel was sealed
customThe methanol was then removed
customthe product chromatographed on silica elueting with 5% methanol in dichloromethane

Sources & evidence

ORD record: ord-a7ef4fa55d9b49199fcee666f34f4801
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841289B2

Reaction notes

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