Sodium Acetate → HCID 59222993, compound

HRID 2386917Notes

Reaction equation

HRID 2386917 reaction equation
C([O-])(=O)C.[Na+].Cl[C:7]1[C:8]([C:36]([F:39])([F:38])[F:37])=[N:9][CH:10]=[C:11](Cl)[C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23]2[C:32]3[C:27](=[C:28]([F:34])[CH:29]=[CH:30][C:31]=3[F:33])[N:26]=[CH:25][N:24]=2)=[CH:16][CH:15]=1>[OH-].[OH-].[Pd+2].CCO>[F:33][C:31]1[CH:30]=[CH:29][C:28]([F:34])=[C:27]2[C:32]=1[C:23]([NH:22][CH2:21][CH2:20][C:17]1[CH:16]=[CH:15][C:14]([O:13][C:12]3[CH:11]=[CH:10][N:9]=[C:8]([C:36]([F:39])([F:37])[F:38])[CH:7]=3)=[CH:19][CH:18]=1)=[N:24][CH:25]=[N:26]2

Participants

5

Reactant 2

HCID 517045Sodium AcetateHCID 59222940HCID 59222940, compound

Product 1

HCID 59222993HCID 59222993, compoundYield 39.7%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 702EthanolSolvent

Procedure

To a suspension of 20% Pd(OH)2 (500 mg) and sodium acetate (368 mg, 4.5 mmol) and absolute EtOH (100 mL) under N2 in a 230 mL Corning shaker bottle was added {2-[4-(3,5-dichloro-2-trifluoromethylpyridin-4-yloxy)-phenyl]-ethyl}-(5,8-difluoroquinazolin-4-yl)-amine (1.15 g, 2.2 mmol). After deaerating, the bottle was charged with H2 (57 psig initial pressure) and shaken at room temp on Parr apparatus. After 24 h, another aliquot of 20% Pd(OH)2 was added, and the bottle was recharged with H2. After another 24 h, the reaction mixture was degassed, placed under nitrogen gas, and then filtered through Celite. The filtrate was evaporated and the residue was purified via preparative reverse phase LC (70% CH3CN/H2O, 0.5% H3PO4 eluant) to provide 390 mg of (5,8-difluoroquinazolin-4-yl)-{2-[4-(2-trifluoromethylpyridin-4-yloxy)-phenyl]-ethyl}-amine as an off-white powder, M.P. 95-96°. 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1 H), 8.56 (d, J=5.7 Hz, 1 H), 7.40-7.31 (m, 3 H), 7.19 (d, J=2.4 Hz, 1 H), 7.10-7.05 (m, 2 H), 7.04-6.95 (m, 2 H), 6.73 (dt, J=16.6, 5.4 Hz, 1 H), 3.97 (q, J=6.9 Hz, 2 H), 3.09 (t, J=7.1 Hz, 1 H); MS: m/z 446.

Workup

  1. additionthe bottle was charged with H2 (57 psig initial pressure) and
  2. waitAfter another 24 h
  3. customthe reaction mixture was degassed
  4. filtrationfiltered through Celite
  5. customThe filtrate was evaporated
  6. customthe residue was purified via preparative reverse phase LC (70% CH3CN/H2O, 0.5% H3PO4 eluant)

Sources & evidence

ORD record
ord-f3b03f54c9154727bdbc7d4ad3c0ae30
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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