Methanol → HCID 178517843, compound

HRID 1801896Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]2[O:26]C(=O)O[C:23]2=O)=[CH:18][CH:17]=1.C[O-].[Na+].CO>C1COCC1>[F:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([OH:26])[C:23]2[N:6]=[C:4]([OH:5])[C:3]3[C:2](=[CH:10][C:9]([C:11]([F:12])([F:13])[F:14])=[CH:8][CH:7]=3)[N:1]=2)=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To 2-amino-4-(trifluoromethyl)benzamide (840 mg, 4.16 mmol), in THF (15 mL) was added 5-(4-fluorophenyl)-1,3-dioxolane-2,4-dione from Example 16 (1225 mg, 6.24 mmol) and the mixture was heated at 50° C. for 4 h. The solvent was evaporated and the crude 2-(2-(4-fluorophenyl)-2-hydroxyacetamido)-4-(trifluoromethyl)benzamide was dissolved in MeOH (10 mL), added 0.5 M sodium methoxide in MeOH (2.5 mL, 1.25 mmol) and the reaction mixture was heated at 50° C. for 1 h. The solvent was evaporated and then 1N hydrochloric acid was added. The mixture was extracted with EtOAc and the organic phase was dried over sodium sulfate and concentrated in vacuo to afford crude 2-((4-fluorophenyl)(hydroxy)methyl)-7-(trifluoromethyl)quinazolin-4-ol, which was used in next reaction without purification. LC-MS (ESI) m/z 339 (M+Na)+.

Workup

customThe solvent was evaporated
dissolutionthe crude 2-(2-(4-fluorophenyl)-2-hydroxyacetamido)-4-(trifluoromethyl)benzamide was dissolved in MeOH (10 mL)
temperaturethe reaction mixture was heated at 50° C. for 1 h
customThe solvent was evaporated
addition1N hydrochloric acid was added
extractionThe mixture was extracted with EtOAc
dry with materialthe organic phase was dried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-18f001e606954f7e9a23b49e233d0bfc
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349851B2

Reaction notes

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