Triethylamine → 6-Quinazolinecarboxylic acid, 1,2,3,4-tetrahydro-5,7-dimethyl-2,4-dioxo-1-(2-(1-piperidinyl)ethyl)-3-(2-(trifluoromethyl)phenyl)-, ethyl ester

HRID 1995649Notes

Reaction equation

HRID 1995649 reaction equation
C(N(CC)CC)C.[F:8][C:9]([F:20])([F:19])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]=[C:17]=[O:18].Cl.Cl.[CH2:23]([O:25][C:26]([C:28]1[C:29]([CH3:47])=[C:30]([C:34]([NH:38][CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]2)=[CH:35][C:36]=1[CH3:37])[C:31](O)=[O:32])=[O:27])[CH3:24]>C(OCC)C>[CH2:23]([O:25][C:26]([C:28]1[C:29]([CH3:47])=[C:30]2[C:34](=[CH:35][C:36]=1[CH3:37])[N:38]([CH2:39][CH2:40][N:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)[C:17](=[O:18])[N:16]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[C:9]([F:8])([F:19])[F:20])[C:31]2=[O:32])=[O:27])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 167942-(Trifluoromethyl)phenyl isocyanateHCID 86739030HCID 86739030, compound

Product 1

HCID 30672866-Quinazolinecarboxylic acid, 1,2,3,4-tetrahydro-5,7-dimethyl-2,4-dioxo-1-(2-(1-piperidinyl)ethyl)-3-(2-(trifluoromethyl)phenyl)-, ethyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Triethylamine (0.58 g) and o-(trifluoromethyl)phenyl isocyanate (0.53 g) were added to a solution of the benzoic acid described above (1.2 g) in diethyl ether (20 ml), and the mixture was refluxed for 4 hours. After evaporating the solvent, the residue was dissolved in ethanol (20 ml) containing 10% hydrogen chloride. The solution was refluxed for one hour and then concentrated. The concentrate was diluted with water and extracted with CHCl3, and the CHCl3 extracts were combined, washed successively with 10% aqueous Na2CO3 solution and brine, and dried over anhydrous Na2SO4. The solvent was evaporated, and the residue was recrystallized from diethyl ether-n-hexane to give 6-ethoxycarbonyl-5,7-dimethyl-1-(2-piperidinoethyl)-3-[2-(trifluoromethyl)phenyl]-2,4(1H,3H)-quinazolinedione (1.1 g, 72%) melting at 144°-145° C. MS: m/e, 517(M+), 498, 472, 433, 406. NMR: δ (ppm. CDCl3), 1.40 (3H, t), 1.50 (6H, b), 2.45 (3H, s), 2.52 (6H, t), 2.70 (3H, s), 4.30 (2H, t), 4.45 (2H, q), 7.10-7.80 (5H, m).

Workup

  1. temperaturethe mixture was refluxed for 4 hours
  2. customAfter evaporating the solvent
  3. dissolutionthe residue was dissolved in ethanol (20 ml)
  4. additioncontaining 10% hydrogen chloride
  5. temperatureThe solution was refluxed for one hour
  6. concentrationconcentrated
  7. additionThe concentrate was diluted with water
  8. extractionextracted with CHCl3
  9. washwashed successively with 10% aqueous Na2CO3 solution and brine
  10. dry with materialdried over anhydrous Na2SO4
  11. customThe solvent was evaporated
  12. customthe residue was recrystallized from diethyl ether-n-hexane

Sources & evidence

ORD record
ord-0a722b5388b34013bb5917fc7c18d026
Source dataset
uspto-grants-1983_09
Patent number
US04405623

Reaction notes

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