Chloroacetonitrile → 7-chloro-2-(chloromethyl)-6-methylquinazolin-4(3H)-one

HRID 47849Notes

Reaction equation

HRID 47849 reaction equation
[Na].[Cl:2][CH2:3][C:4]#[N:5].[NH2:6][C:7]1[CH:15]=[C:14]([Cl:16])[C:13]([CH3:17])=[CH:12][C:8]=1[C:9](O)=[O:10]>CO>[Cl:16][C:14]1[CH:15]=[C:7]2[C:8]([C:9](=[O:10])[NH:5][C:4]([CH2:3][Cl:2])=[N:6]2)=[CH:12][C:13]=1[CH3:17]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 5360545SodiumHCID 110953002-Amino-4-chloro-5-methylbenzoic acid

Product 1

HCID 1354761257-chloro-2-(chloromethyl)-6-methylquinazolin-4(3H)-oneYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a flask containing sodium (36 mg) was added anhydrous MeOH (5 ml). Chloroacetonitrile (0.520 g, 6.9 mmol) was then added and the clear solution was stirred at room temperature for 30 min under argon. A solution of 2-amino-4-chloro-5-methylbenzoic acid (1.13 g, 6.0 mmol) in anhydrous methanol (25 ml) was then added with a syringe via a rubber septum. The reaction mixture was stirred at room temperature for 2 hours under argon, then it was fitted with a condenser and placed in an oil bath preheated to 80° C. Stirring was continued at this temperature for 2 hours under argon, then the reaction mixture was allowed to cool to room temperature. The precipitate was collected by filtration, washed with methanol (10 ml), and water (10 ml), and dried in vacuo over P2O5 to afford a grey solid (1.0 g, 69%), mp 287-290° C.; 1H-NMR (DMSO-d6) 2.47 (s, 3H, 6-CH3), 4.53 (s, 2H, CH2Cl), 7.75, 8.08 (2×s, 2H, 5-H and 8-H); 12.60 (s, 1H, N3—H); MS (FAB, m/z) 243, 244, 245 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 hours under argon
  2. customit was fitted with a condenser
  3. customplaced in an oil bath
  4. custompreheated to 80° C
  5. stirringStirring
  6. waitwas continued at this temperature for 2 hours under argon
  7. temperatureto cool to room temperature
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with methanol (10 ml), and water (10 ml)
  10. dry with materialdried in vacuo over P2O5

Sources & evidence

ORD record
ord-d10365f6c786439e96dd407dbf02784f
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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