1H-Pyrazol-3-amine, 5-methyl- → methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate

HRID 473211Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]([F:25])([F:24])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=2)[N:3]=1.[CH3:26][C:27]1[NH:31][N:30]=[C:29]([NH2:32])[CH:28]=1>O1CCOCC1>[F:24][C:16]([F:25])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:4]1[N:3]=[C:2]([NH:32][C:29]2[CH:28]=[C:27]([CH3:26])[NH:31][N:30]=2)[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of methyl 4-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline-8-carboxylate (27 g, 65.5 mmol) in dioxane (300 mL) was added 5-methyl-1H-pyrazol-3-amine (12.7 g, 131 mmol) and the mixture was stirred at 50° C. overnight. The mixture was concentrated and the residue was triturated with water (1 L). The solid was collected by filtration, washed with water, and dried in air to afford methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate as a solid. (26.7 g, 95%). LC-MS (ESI) m/z 429.6 (M+H+). 1H NMR (500 MHz, DMSO-d6) δ 12.23 (1H, s), 10.86 (1H, s), 8.82 (1H, d, J=8.2 Hz), 8.67 (1H, d, J=2.6 Hz), 7.99 (3H, m), 7.68 (1H, t, J=8.0 Hz), 6.05 (1H, s), 3.83 (3H, s), 2.19 (3H, s).

Workup

concentrationThe mixture was concentrated
customthe residue was triturated with water (1 L)
filtrationThe solid was collected by filtration
washwashed with water
customdried in air

Sources & evidence

ORD record: ord-bf6be38a749145e1865d7e34c365c8ba
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633207B2

Reaction notes

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