Acetic Acid → HCID 178505731, compound

HRID 473135Notes

Reaction equation

HRID 473135 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]([F:21])([F:20])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.CC(O)=O>CN(C=O)C>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:4]1[N:3]=[C:2]([NH:36][C:33]2[CH:34]=[CH:35][NH:31][N:32]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 866626934-Chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolineHCID 178418806HCID 178418806, compound

Product 1

HCID 178505731HCID 178505731, compoundYield 13.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline (100 mg, 0.32 mmol) was added a solution of KI (20 mg, 0.12 mmol), DIEA (0.068 mL, 0.39 mmol), and 1H-pyrazol-3-amine (40 mg, 0.48 mmol) in DMF (2 mL). The mixture was stirred overnight at rt. AcOH (0.14 mL) was added and the mixture was purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=0.05% AcOH/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(1H-pyrazol-3-yl)quinazolin-4-amine (15 mg, 13%). 1H NMR (300 MHz, DMSO-d6) δ 12.52 (br s, 1H), 10.82 (br s, 1H), 8.53-8.86 (m, 2H), 7.77-8.13 (m, 4H), 7.57-7.74 (m, 2H), 6.50 (br s, 1H); LC-MS (ESI) m/z 357 (M+H)+.

Workup

  1. customthe mixture was purified by preparative HPLC (Varian diphenyl reverse phase column
  2. washeluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=0.05% AcOH/H2O)

Sources & evidence

ORD record
ord-456b8bb669e2401f97e2a27e49b60583
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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