Diisopropylethylamine → (8-fluoro-4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)(4-fluorophenyl)methanone

HRID 625807Notes

Reaction equation

HRID 625807 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([F:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:14])[N:3]=1.[CH3:22][C:23]1[NH:27][N:26]=[C:25]([NH2:28])[CH:24]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:12][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)=[O:14])[N:3]=[C:2]2[NH:28][C:25]1[CH:24]=[C:23]([CH3:22])[NH:27][N:26]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 86649065(4-Chloro-8-fluoroquinazolin-2-yl)(4-fluorophenyl)methanone

Product 1

HCID 46893384(8-fluoro-4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)(4-fluorophenyl)methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (4-chloro-8-fluoroquinazolin-2-yl)(4-fluorophenyl)methanone (0.4 g, 1.32 mmol), 5-methyl-1H-pyrazol-3-amine (0.15 g, 1.58 mmol), DIEA (0.69 mL, 4.0 mmol), and KI (0.24 g, 1.45 mmol) in DMF (8 mL) was stirred at rt for 20 h. The mixture was diluted with H2O (35 mL), and the precipitated solid was collected by filtration, washed with H2O, and triturated with MeOH at 0° C. A portion of the resulting solid was purified by preparative reverse phase HPLC to afford (8-fluoro-4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)(4-fluorophenyl)methanone. 1H NMR (300 MHz, DMSO-d6) δ 2.19 (s, 3H), 6.52 (s, 1H), 7.41 (t, 2H), 7.64-7.80 (m, 2H), 8.11 (t, 2H), 8.57 (d, 1H), 10.84 (s, 1H), 12.27 (br s, 1H); LC-MS (ESI) m/z 366 (M+H)+.

Workup

  1. filtrationthe precipitated solid was collected by filtration
  2. washwashed with H2O
  3. customtriturated with MeOH at 0° C
  4. customA portion of the resulting solid was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-b34233a1bdaf456a914dbc0156c45f2e
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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