Diisopropylethylamine → (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

HRID 1801881Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[O:13])[N:3]=1.CCN(C(C)C)C(C)C.[CH3:30][C:31]1[NH:35][N:34]=[C:33]([NH2:36])[CH:32]=1>CN(C=O)C>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]([C:4]2[N:3]=[C:2]([NH:36][C:33]3[CH:32]=[C:31]([CH3:30])[NH:35][N:34]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:13])=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of (4-chloroquinazolin-2-yl)(4-fluorophenyl)methanone (84 mg, 0.30 mmol) in DMF (3mL) were added DIEA (0.103 mL, 0.6 mmol) and 5-methyl-1H-pyrazol-3-amine (88 mg, 0.9 mmol at rt. The reaction mixture was heated at 40° C. overnight. The reaction was quenched by adding water and the yellow precipitate was collected by filtration and washed with water. The crude product was purified by silica gel chromatography eluting with DCM/MeOH to give (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone (30 mg, 29%). 1H NMR (300 MHz, DMSO-d6) δ 2.19 (s, 3H), 6.54 (s, 1H), 7.40 (m, 2H), 7.68 (t, 1H), 7.9-7.7 (m, 2H), 8.08 (m, 2H), 8.74 (d, 1H), 10.66 (s, 1H), 12.20 (s, 1H);LC-MS (ESI) m/z 348 (M+H)+.

Workup

customThe reaction was quenched
additionby adding water
filtrationthe yellow precipitate was collected by filtration
washwashed with water
customThe crude product was purified by silica gel chromatography
washeluting with DCM/MeOH

Sources & evidence

ORD record: ord-06d5cb0cdecd437299fe287b61297735
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349851B2

Reaction notes

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