Potassium Iodide → (5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

HRID 473123Notes

Reaction equation

HRID 473123 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][N:15]=2)=[O:13])[N:3]=1.[CH3:21][C:22]1[NH:26][N:25]=[C:24]([NH2:27])[CH:23]=1.CCN(C(C)C)C(C)C.[I-].[K+]>CN(C)C=O.O>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]([C:4]2[N:3]=[C:2]([NH:27][C:24]3[CH:23]=[C:22]([CH3:21])[NH:26][N:25]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:13])=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 86662692(4-Chloroquinazolin-2-yl)(5-fluoropyridin-2-yl)methanone

Product 1

HCID 56848496(5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanoneYield 6.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of (4-chloroquinazolin-2-yl)(5-fluoropyridin-2-yl)methanone (244 mg, 0.85 mmol) and 5-methyl-3-aminopyrazole (99 mg, 1.02 mmol) in N,N-dimethylformamide (3 mL) were added DIEA (0.3 mL, 4.22 mmol) and potassium iodide (141 mg, 0.85 mmol) and the mixture was stirred at rt for 15 h and then at 60° C. for 2.5 h. The mixture was allowed to cool to rt, and then water was added. The precipitated solid was collected by filtration. A portion of the solid (180 mg) was purified by preparative reverse-phase HPLC eluting with 30% to 70% acetonitrile/0.05% aq HOAc to afford (5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone (19.6 mg). 1H NMR (300 MHz, CDCl3) δ 12.19 (s, 1H), 10.65 (s, 1H), 8.72-8.69 (m, 2H), 8.26 (m, 1H), 8.00 (td, J=3 Hz, J=8.7 Hz, 1H), 7.92-7.80 (m, 2H), 7.66 (t, J=7.5 Hz, 1H), 6.34 (s, 1H), 2.16 (s, 3H); LC-MS (ESI) m/z 349 (M+H)+.

Workup

  1. waitat 60° C. for 2.5 h
  2. temperatureto cool to rt
  3. filtrationThe precipitated solid was collected by filtration
  4. customA portion of the solid (180 mg) was purified by preparative reverse-phase HPLC
  5. washeluting with 30% to 70% acetonitrile/0.05% aq HOAc

Sources & evidence

ORD record
ord-f074a5afe0fa41d08c90ed8b29ba465c
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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