Phosphorus oxychloride → HCID 86649058, compound

HRID 1424435Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=O)[NH:14][C:15]([C:19](=[O:27])[C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:31])=O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:31])=[N:14][C:15]([C:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[O:27])=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 56 °C

Procedure

To phosphorous oxychloride (10 mL) cooled to 5° C. was added portionwise 7-(benzyloxy)-2-(4-fluorobenzoyl)quinazolin-4(3H)-one (500 mg, 1.34 mmol) followed by the addition of DMF (4 drops). The mixture was warmed to 56° C. over 10 min and held at this temperature for 2 min, then the heating bath was removed. The mixture was concentrated, and the residue was diluted with EtOAc, then the solution was and washed with cold water, saturated sodium bicarbonate (aq), brine, and dried over sodium sulfate. The solution was concentrated to afford (7-(benzyloxy)-4-chloroquinazolin-2-yl)(4-fluorophenyl)methanone as an off-white solid (380 mg, 72%). 1H NMR (300 MHz, DMSO-d6) δ ppm 5.40 (s, 2H) 7.37-7.45 (m, 5H) 7.52-7.55 (m, 2H) 7.66-7.71 (m, 2H) 8.09-8.14 (m, 2H) 8.31 (d, J=9.04 Hz, 1H). LC-MS (ESI) m/z 393 (M+H)+.

Workup

customthe heating bath was removed
concentrationThe mixture was concentrated
additionthe residue was diluted with EtOAc
washwashed with cold water, saturated sodium bicarbonate (aq), brine
dry with materialdried over sodium sulfate
concentrationThe solution was concentrated

Sources & evidence

ORD record: ord-7c068058da7d47a4bc4ff8595f771a22
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927711B2

Reaction notes

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