Potassium Fluoride → Ethyl 2-fluoro-4-[6-(1-trityl-1H-pyrazol-4-yl)-quinazolin-4-yl]benzoate

HRID 1792609Notes

Reaction equation

HRID 1792609 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[C:12]1[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:14]([F:23])[CH:13]=1.[C:24]([N:43]1[CH:47]=[C:46](B(O)O)[CH:45]=[N:44]1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[F-].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN(C)C=O>[F:23][C:14]1[CH:13]=[C:12]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:46]4[CH:45]=[N:44][N:43]([C:24]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[CH:47]=4)[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:22]=[CH:21][C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

8

Reactant 4

HCID 522689Potassium FluorideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22031224Ethyl 4-(6-chloroquinazolin-4-yl)-2-fluorobenzoateHCID 22031737(1-Trityl-1H-pyrazol-4-yl)boronic acid

Product 1

HCID 22031192Ethyl 2-fluoro-4-[6-(1-trityl-1H-pyrazol-4-yl)-quinazolin-4-yl]benzoateYield 70.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

0.64 g ethyl 4-(6-chloroquinazolin-4-yl)-2-fluorobenzoate (compound in Production Example 385), 1.02 g 1-trityl-1H-4-pyrazolylboronic acid, 0.34 g potassium fluoride, 43 mg palladium (II) acetate, 0.11 g 2-(di-t-butylphosphino)biphenyl, 20 mL N,N-dimethylformamide and 2 mL water were heated at 70° C. for 24 hours under nitrogen atmosphere. Water was added thereto, the reaction solution was filtered, and crystals collected by filtration were washed with water. The crystals were dissolved in dichloromethane, washed with water and dried over sodium sulfate. The solvent was evaporated, and the residue was purified by NH silica gel column chromatography (hexane/ethyl acetate), to give 0.82 g of the title compound (pale yellow crystals).

Workup

  1. filtrationthe reaction solution was filtered
  2. filtrationcrystals collected by filtration
  3. washwere washed with water
  4. dissolutionThe crystals were dissolved in dichloromethane
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated
  8. customthe residue was purified by NH silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a7c568d94a0f4e84ae663770a21c8249
Source dataset
uspto-grants-2006_07
Patent number
US07074801B1

Reaction notes

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