Potassium Iodide → HCID 46892494, compound

HRID 625751Notes

Reaction equation

HRID 625751 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[O:17])[N:3]=1.CCN(C(C)C)C(C)C.[CH3:34][C:35]1[NH:39][N:38]=[C:37]([NH2:40])[CH:36]=1.[I-].[K+]>CN(C=O)C.O>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]([C:4]2[N:3]=[C:2]([NH:40][C:37]3[CH:36]=[C:35]([CH3:34])[NH:39][N:38]=3)[C:11]3[C:6](=[CH:7][C:8]([C:12]([F:13])([F:14])[F:15])=[CH:9][CH:10]=3)[N:5]=2)=[O:17])=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 86649051HCID 86649051, compound

Product 1

HCID 46892494HCID 46892494, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To (4-chloro-7-(trifluoromethyl)quinazolin-2-yl)(4-fluorophenyl)methanone (1 g, 2.82 mmol) in DMF (10 mL) were added DIEA (0.49 mL, 2.82 mmol), 5-methyl-1H-pyrazol-3-amine (823 mg, 8.47 mmol), and potassium iodide (468 mg, 2.82 mmol) and the mixture was stirred at rt for 2 h. To the reaction mixture was added water followed by extraction with EtOAc. The organic phases were dried over sodium sulfate. The solvent was concentrated and the residue was dried under high vacuum overnight. The crude solid (240 mg) was purified on reverse-phase preparative HPLC (elution gradient of 40-90% acetonitrile in water with 0.05% acetic acid) to afford (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)-7-(trifluoromethyl)quinazolin-2-yl)methanone as a yellow solid (40 mg, 16%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.2 (s, 3H) 6.55 (s, 1H) 7.35-7.5 (m, 3H) 7.9-8.0 (m, 1H) 8.05-8.3 (m, 4H) 11.1 (s, 1H) 12.25 (s, 1H) LC-MS (ESI) m/z 416 (M+H)+.

Workup

  1. extractionfollowed by extraction with EtOAc
  2. dry with materialThe organic phases were dried over sodium sulfate
  3. concentrationThe solvent was concentrated
  4. customthe residue was dried under high vacuum overnight
  5. customThe crude solid (240 mg) was purified on reverse-phase preparative HPLC (elution gradient of 40-90% acetonitrile in water with 0.05% acetic acid)

Sources & evidence

ORD record
ord-abfc52eeef1c4ac28ff0ff519b019e4d
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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