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

HRID 1424466Notes

Reaction equation

HRID 1424466 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-3939ea3a80904b849a5ea1cd06b2396c
Source dataset
uspto-grants-2015_01
Patent number
US08927711B2

Reaction notes

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