Oxalyl chloride → 2-(3-(Benzyloxy)phenyl)-4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazoline

HRID 61670Notes

Reaction equation

HRID 61670 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[NH:24][C:23](=O)[C:22]3[C:17](=[CH:18][C:19]([O:31][CH3:32])=[C:20]([O:26][CH2:27][CH2:28][O:29][CH3:30])[CH:21]=3)[N:16]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:36])=O>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:24]=[C:23]([Cl:36])[C:22]3[C:17](=[CH:18][C:19]([O:31][CH3:32])=[C:20]([O:26][CH2:27][CH2:28][O:29][CH3:30])[CH:21]=3)[N:16]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chloride2×HCID 1362032432-(3-(benzyloxy)phenyl)-7-methoxy-6-(2-methoxyethoxy)quinazolin-4(3H)-one

Product 1

HCID 593619262-(3-(Benzyloxy)phenyl)-4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazolineYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(3-(benzyloxy)phenyl)-7-methoxy-6-(2-methoxyethoxy)quinazolin-4(3H)-one (3.28 g, 7.58 mmol) in CH2Cl2 (100 mL) was added oxalyl chloride (2.20 mL, 24.8 mmol) and 2 drops of DMF. The mixture was stirred at RT for 6 h. An additional aliquot of oxalyl chloride (1.20 mL, 13.5 mmol) was added. Stirring was continued at RT overnight, upon which the mixture was concentrated in vacuo, taken up in CHCl3 (100 mL) and washed with sat. NaHCO3 (3×50 mL), water (2×50 mL) and brine (1×50 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give 2-(3-(benzyloxy)phenyl)-4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazoline (1.52 g, 3.37 mmol, 45%). MS 451 (M+1 Cl isotope pattern). HPLC retention time 10.84 mins. (10-95-13 method).

Workup

  1. stirringStirring
  2. waitwas continued at RT overnight, upon which
  3. concentrationthe mixture was concentrated in vacuo
  4. washwashed with sat. NaHCO3 (3×50 mL), water (2×50 mL) and brine (1×50 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2c993e9f00a84011bf9c746ccd1ff0f1
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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