Hydrochloric Acid → 2-(pyridin-3-yl)-4-(2-chloro-4-fluorophenyl)-4,6,7,8-tetrahydroquinazolin-5(1H)-one

HRID 1929538

Reaction equation

HRID 1929538 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([NH2:10])=[NH:9])[CH:3]=1.[Cl:11][C:12]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:13]=1[CH:14]=O.[C:21]1(=O)[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[CH2:22]1.C([O-])(=O)C.[Na+].Cl>C(O)C.O.C(OCC)(=O)C>[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[NH:10][C:21]3[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[C:22]=3[CH:14]([C:13]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:12]=3[Cl:11])[N:9]=2)[CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 104341,3-CyclohexanedioneHCID 1450242-Chloro-4-fluorobenzaldehydeHCID 202042Nicotinamidine hydrochlorideHCID 517045Sodium Acetate

Product 1

HCID 250302972-(pyridin-3-yl)-4-(2-chloro-4-fluorophenyl)-4,6,7,8-tetrahydroquinazolin-5(1H)-oneYield 27%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-pyridinecarboxamidine hydrochloride (Schaefer F. C., Peters G. A., et al. J. Org. Chem.; 1961; 26(2); 412-418.) 2.164 mmol, 2-chloro-4-fluorobenzaldehyde 2.164 mmol, 1,3-cyclohexanedione 2.164 mmol and sodium acetate 3.2 mmol were reacted in 8 ml of anhydrous ethanol under reflexing for 18 hr, condensed, to which ethyl acetate, water and 1N HCl were added and then the layers were separated. The water layer was adjusted with concentrated NaOH solution until the pH to be basic, then ethyl acetate was added and extracted twice. The organic layers were combined, dried over anhydrous sodium sulfate and separated by column chromatography to obtain a yellow solid of 0.21 g (yield 27%); 1H-NMR (400 MHz, CDCl3) δ 2.13-2.17 (2H, m, CH2); 2.43-2.51 (2H, m, CH2); 2.63-2.83 (2H, m, CH2); 6.06 (1H, s, CH); 7.15-7.22 (2H, m, ArH); 7.34-7.38 (1H, m, ArH); 8.07-8.09 (1H, m, ArH); 8.70-8.71 (1H, m, ArH); 8.89 (1H, m, ArH). MS (HREI) 355.0887 (M+).

Workup

  1. customcondensed
  2. customthe layers were separated
  3. additionethyl acetate was added
  4. extractionextracted twice
  5. dry with materialdried over anhydrous sodium sulfate
  6. customseparated by column chromatography
  7. customto obtain a yellow solid of 0.21 g (yield 27%)

Sources & evidence

ORD record
ord-c7f175dbfd0c43549c510f6913488306
Source dataset
uspto-grants-2012_05
Patent number
US08188091B2

Linked notes

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