Oxalyl chloride → N-(3-isopropylisoxazol-5-yl)-2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetamide

HRID 1690500Notes

Reaction equation

HRID 1690500 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](O)=[O:24])=[CH:18][CH:17]=1.C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[CH:34]=1>C(Cl)Cl>[CH:38]([C:35]1[CH:34]=[C:33]([NH:32][C:23](=[O:24])[CH2:22][C:19]2[CH:18]=[CH:17][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)=[CH:21][CH:20]=2)[O:37][N:36]=1)([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 65578Oxalyl chlorideHCID 21152083-(Propan-2-yl)-1,2-oxazol-5-amineHCID 669066322-[4-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl]acetic acid

Product 1

HCID 66906894N-(3-isopropylisoxazol-5-yl)-2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetamideYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetic acid (0.3 g) and oxalyl chloride (3.73 ml) was heated at 60° C. for 30 minutes. The excess of oxalyl chloride was evaporated. Pyridine (0.43 ml) was added to a stirred mixture of the 2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetyl chloride so obtained, 5-amino-3-isopropylisoxazole (0.148 g) and methylene chloride (30 ml). The resultant mixture was stirred at ambient temperature for 30 minutes. The mixture was evaporated and the residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and ethyl acetate as eluent. There was thus obtained the title compound (0.183 g); 1H NMR: (DMSOd6) 1.89 (d, 6H), 2.92 (m, 1H), 3.75 (s, 2H), 3.97 (s, 3H), 4.0 (s, 3H), 6.18 (s, 1H), 7.26 (d, 2H), 7.39 (s, 1H), 7.41 (d, 2H), 7.55 (s, 1H), 8.53 (s, 1H), 11.83 (br s, 1H); Mass Spectrum: M+H+ 449.

Workup

  1. customThe excess of oxalyl chloride was evaporated
  2. additionPyridine (0.43 ml) was added to a stirred mixture of the 2-[4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]acetyl chloride
  3. customso obtained
  4. customThe mixture was evaporated
  5. customthe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of methylene chloride and ethyl acetate as eluent

Sources & evidence

ORD record
ord-8a2d97a70c3b4abeb72201fdd4192e6e
Source dataset
uspto-grants-2012_04
Patent number
US08153643B2

Reaction notes

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