Chloroacetyl chloride → 5-Chloro-2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one

HRID 2074512Notes

Reaction equation

HRID 2074512 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14])=[O:5].[Cl:20][CH2:21][C:22](Cl)=O>CC(O)=O>[Cl:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:2]2[C:3]=1[C:4](=[O:5])[N:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14])[C:22]([CH2:21][Cl:20])=[N:1]2

Participants

4

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 223165492-amino-6-chloro-N-(2-methoxyphenyl)benzamide

Product 1

HCID 223165905-Chloro-2-chloromethyl-3-(2-methoxyphenyl)-3H-quinazolin-4-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-amino-6-chloro-N-(2-methoxyphenyl)benzamide (4.0813 g, 14.75 mmol) in AcOH (39 mL) was added dropwise chloroacetyl chloride (3.6 mL, 45.2 mmol, 3 eq), and then the mixture was stirred at 110° C. for 3 h. The mixture was cooled to rt and concentrated under reduce pressure. The residue was dissolved in H2O and neutralized with K2CO3. The oily product was extracted with CH2Cl2 (3 times). The combined organic layers were dried with K2CO3, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on a 120 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 20 min as eluent to provide 5-chloro-2-(chloromethyl)-3-(2-methoxyphenyl)quinazolin-4(3H)-one as off-white solid. 1H NMR (DMSO-d6) δ ppm 7.83 (1 H, t, J=7.9 Hz), 7.69-7.74 (1 H, m), 7.64 (1 H, dd, J=7.9, 0.9 Hz), 7.51-7.58 (1 H, m), 7.47 (1 H, dd, J=7.7, 1.6 Hz), 7.26 (1 H, d, J=8.3 Hz), 7.09-7.17 (1 H, m), 4.28 (2 H, dd, J=51.8, 12.5 Hz), 3.77 (3 H, s). Mass Spectrum (ESI) m/e=335.0 and 337.0 (M+1).

Workup

  1. temperatureThe mixture was cooled to rt
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in H2O and neutralized with K2CO3
  4. extractionThe oily product was extracted with CH2Cl2 (3 times)
  5. dry with materialThe combined organic layers were dried with K2CO3
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on a 120 g of Redi-Sep™ column
  9. customover 20 min

Sources & evidence

ORD record
ord-70aaa99c2a2f468a8ef8689649a8d3a6
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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