Ethyl Acetate → HCID 178517774, compound

HRID 473143Notes

Reaction equation

[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]([O-])=O.[Na+].[NH2:15][C:16]1[CH:24]=[C:23]([Br:25])[CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19].C[Si](OP(=O)=O)(C)C.CCOC(C)=O>O>[Br:25][C:23]1[CH:24]=[C:16]2[C:17]([C:18]([OH:19])=[N:20][C:3]([C:2]([F:13])([F:1])[C:6]3[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=3)=[N:15]2)=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (2.05 g, 9.62 mmol) and 2-amino-4-bromobenzamide (1.89 g, 8.75 mmol) was added trimethylsilyl polyphosphate (˜15 mL) and the mixture was stirred overnight at 120° C. Equal volumes of EtOAc and water were added and the resulting solution was stirred for 1 h. The EtOAc layer was washed with brine, dried over Na2SO4 and then concentrated under reduced pressure. Et2O was added and evaporated. Trituration of the residue with hexanes, followed by collection of the solid by filtration afforded 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol (2.49 g, 77%). 1H NMR (300 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.76 (s, 1H), 7.97-8.07 (m, 2H), 7.88 (d, J=8.3 Hz, 1H), 7.69-7.81 (m, 2H);

Workup

stirringthe resulting solution was stirred for 1 h
washThe EtOAc layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
additionEt2O was added
customevaporated
filtrationTrituration of the residue with hexanes, followed by collection of the solid by filtration

Sources & evidence

ORD record: ord-892dd47a47fb4d819fccf96d561ff847
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633207B2

Reaction notes

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