Sodium Acetate → 4'-[[[2-Trifluoromethyl-4-quinazolinyl]amino]methyl][1,1'-biphenyl]-2-carboxylic acid methyl ester

HRID 2082018Notes

Reaction equation

HRID 2082018 reaction equation
C([O-])(=O)C.[Na+].[NH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:20]([O:22][CH3:23])=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:10][CH:9]=1.Cl[C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[N:26]=1>O1CCCC1>[CH3:23][O:22][C:20]([C:15]1[C:14]([C:11]2[CH:12]=[CH:13][C:8]([CH2:7][NH:6][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]=[C:27]([C:35]([F:37])([F:38])[F:36])[N:26]=3)=[CH:9][CH:10]=2)=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:21]

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 1393434Methyl 2-[4-(aminomethyl)phenyl]benzoateHCID 14754354-Chloro-2-(trifluoromethyl)quinazoline

Product 1

HCID 152338194'-[[[2-Trifluoromethyl-4-quinazolinyl]amino]methyl][1,1'-biphenyl]-2-carboxylic acid methyl esterYield 110.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium acetate (2.34 g), 4'-aminomethyl(1,1'-biphenyl)-2-carboxylic acid, methyl ester (1.99 g) and 1.66 g of 4-chloro-2-trifluoromethylquinazoline were added to 50 mL of tetrahydrofuran. The resulting suspension was stirred at 40°-50° C. for 72 hours. All the THF was removed by evaporation and the residue was partitioned between ethyl acetate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel chromatography to yield. 3.46 g (40%) of the desired product (M.P.=135°-142° C.): 1H NMR (DMSO-d6, 400 MHz) δ9.43 (t, J=6 Hz, 1H), 8.41 (d, 7.9 Hz, 1H), 7.88 (m, 2H), 7.70 (m, 2H), 7.58 (m, 1H), 7.43 (m, 4H), 7.25 (m, 2H), 4.85 (d, J=5.9 Hz, 2H), 3.56 (s, 3H); positive FAB MS m/e 438 (MH). Anal Calcd for C24H18F3N3O2.0.5H2O: C, 64.57; H, 4.29; N, 9.41. Found: C, 64.83; H, 4.02; N, 9.48.

Workup

  1. customAll the THF was removed by evaporation
  2. customthe residue was partitioned between ethyl acetate and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified on silica gel chromatography
  7. customto yield

Sources & evidence

ORD record
ord-7bdce22cbd0449458bfb71168e3dc0a4
Source dataset
uspto-grants-1993_02
Patent number
US05187168

Reaction notes

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