Sulfuric Acid → 2-(Difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-8-carboxamide

HRID 473193Notes

Reaction equation

[F:1][C:2]([F:24])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:3]1[N:12]=[C:11]([S:13][CH3:14])[C:10]2[C:5](=[C:6]([C:15]#[N:16])[CH:7]=[CH:8][CH:9]=2)[N:4]=1.S(=O)(=O)(O)[OH:26].C(=O)(O)[O-].[Na+]>O>[F:24][C:2]([F:1])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:3]1[N:12]=[C:11]([S:13][CH3:14])[C:10]2[C:5](=[C:6]([C:15]([NH2:16])=[O:26])[CH:7]=[CH:8][CH:9]=2)[N:4]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-8-carbonitrile from Example 35 step C (200 mg, 0.57 mmol) were added concentrated sulfuric acid (2.88 mL) and water (0.32 mL). The mixture was stirred at 65° C. for 1 h and then allowed to cool to rt. The mixture was neutralized by slow addition of saturated aq sodium bicarbonate and then extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-8-carboxamide (191 mg, 92%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.60 (s, 3H) 7.89-8.15 (m, 4H) 8.36-8.44 (m, 1H) 8.62-8.69 (m, 1H) 8.71-8.79 (m, 1H) 9.28-9.39 (m, 1H).

Workup

temperatureto cool to rt
extractionextracted with EtOAc
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-685a1bb01c434cc98a0ab55057a3b7be
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633207B2

Reaction notes

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