Sodium Bicarbonate → [7-(3-Fluoro-benzyloxy)-2-isopropyl-4-oxo-4H-quinazolin-3-yl]-acetonitrile

HRID 7631Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11](=[O:24])[N:12]([CH2:20][C:21]([NH2:23])=O)[C:13]([CH:17]([CH3:19])[CH3:18])=[N:14]2)=[CH:9][CH:8]=1.C(=O)([O-])O.[Na+]>CN(C)C=O.ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11](=[O:24])[N:12]([CH2:20][C:21]#[N:23])[C:13]([CH:17]([CH3:19])[CH3:18])=[N:14]2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a mixture of 2-[7-(3-fluoro-benzyloxy)-2-isopropyl-4-oxo-4H-quinazolin-3-yl]-acetamide (50 mg, 0.14 mmol) in dimethylformamide (0.5 mL), dichloromethane (2 mL) was added N-ethyl-N,N-diispropylamine (26.2 mg, 0.2 mmol) and the resulting mixture cooled to −78° C. Then trifluorosulfonic anhydride (49.6 mg, 0.18 mmol) was added and the reaction mixture allowed to warm up to rt over 30 min. The resulting mixture was then poured into sodium hydrogen carbonate (sat. 5 mL), and the mixture extracted with diethylether (3×5 mL). The combined extracts were then washed with brine, dried and evaporated to leave a light yellow solid. Purification by chromatography (SiO2, EtOAc:heptane 1:1 to 85:15) afforded the title compound (26 mg, 55%) as a white solid. MS: m/e=352.2 (M+H+).

Workup

additionwas added N-ethyl-N,N-diispropylamine (26.2 mg, 0.2 mmol)
temperatureto warm up to rt over 30 min
extractionthe mixture extracted with diethylether (3×5 mL)
washThe combined extracts were then washed with brine
customdried
customevaporated
customto leave a light yellow solid
customPurification by chromatography (SiO2, EtOAc:heptane 1:1 to 85:15)

Sources & evidence

ORD record: ord-29111edc181f4bb49fd521e1721d15d2
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07087612B2

Reaction notes

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