Sodium Acetate → 4'-[[[5,6,7,8-Tetrahydro-2-(trifluoromethyl)-4-quinazolinyl]amino]methyl][1,1'-biphenyl]-2-carboxylic acid

HRID 2254119Notes

Reaction equation

HRID 2254119 reaction equation
Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[NH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([C:30]([OH:32])=[O:31])=[CH:26][CH:27]=[CH:28][CH:29]=2)=[CH:20][CH:19]=1.C([O-])(=O)C.[Na+]>C(O)CCC>[F:13][C:12]([F:15])([F:14])[C:4]1[N:3]=[C:2]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[C:25]([C:30]([OH:32])=[O:31])=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:20][CH:19]=2)[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 152911614'-(Aminomethyl)-biphenyl-2-carboxylic acidHCID 19383098HCID 19383098, compound

Product 1

HCID 98465354'-[[[5,6,7,8-Tetrahydro-2-(trifluoromethyl)-4-quinazolinyl]amino]methyl][1,1'-biphenyl]-2-carboxylic acidYield 59%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

To 10 mL of n-butanol were added 0.526 g of 4-chloro-5,6,7,8-tetrahydro-2-trifluoromethylquinazoline, 0.408 g of 4' aminomethyl-(1,1'-biphenyl)-2-carboxylic acid and 1.1 g of sodium acetate. The resulting mixture was refluxed for 3 days, cooled to room temperature and all solvents were removed by evaporation. The residue was taken up in ethyl acetate and washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated to yield an off-white solid which was purified by silica chromatography to yield the desired product (0.39 g, 59%). The compound was characterized as its sodium salt: 1H NMR (DMSO-d6, 400 MHz) δ 7.88 (t, J=6.0 Hz, 1H), 7.39 (m, 2H), 7.28 (m, 3H), 7.17 (m, 3H), 4.60 (d, J=5.9 Hz, 2H), 2.61 (m, 2H), 2.38 (m, 2H), 1.74 (m, 4H); negative FAB-MS m/e 448(M-H), 426(M-Na). Anal. calcd for C23H19F3N3NaO2.1.0H2O: C, 59.10; H, 4.53; N, 8.99. Found: C, 59.03; H, 4.48; N, 9.09.

Workup

  1. temperatureThe resulting mixture was refluxed for 3 days
  2. customall solvents were removed by evaporation
  3. washwashed with brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto yield an off-white solid which
  8. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-5a776dd3f8a24279b7d8ffee0bf0f075
Source dataset
uspto-grants-1993_08
Patent number
US05234936

Reaction notes

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