Cesium carbonate → 6-(N,N-Diethylcarbamoylmethoxy)-7-methoxy-4-[2-methyl-5-(2-morpholinopyridine-4-carboxamido)anilino]quinazoline

HRID 1357710Notes

Reaction equation

HRID 1357710 reaction equation
Cl[CH2:2][C:3]([N:5]([CH2:8][CH3:9])[CH2:6][CH3:7])=[O:4].[OH:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]2[NH:23][C:24]1[CH:29]=[C:28]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH:34]=2)=[O:32])[CH:27]=[CH:26][C:25]=1[CH3:45].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[CH2:6]([N:5]([CH2:8][CH3:9])[C:3]([CH2:2][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[N:17]=[CH:16][N:15]=[C:14]2[NH:23][C:24]1[CH:29]=[C:28]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([N:39]3[CH2:40][CH2:41][O:42][CH2:43][CH2:44]3)[CH:34]=2)=[O:32])[CH:27]=[CH:26][C:25]=1[CH3:45])=[O:4])[CH3:7]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 16844Chloro-N,N-diethylacetamideHCID 227322826-Hydroxy-7-methoxy-4-[2-methyl-5-(2-morpholinopyridine-4-carboxamido)anilino]quinazoline

Product 1

HCID 227322966-(N,N-Diethylcarbamoylmethoxy)-7-methoxy-4-[2-methyl-5-(2-morpholinopyridine-4-carboxamido)anilino]quinazolineYield 21.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-N,N-diethylacetamide (0.05 g) was added to a mixture of 6-hydroxy-7-methoxy-4-[2-methyl-5-(2-morpholinopyridine-4-carboxamido)anilino]quinazoline (0.15 g), cesium carbonate (0.3 g) and dimethylacetamide (2 ml) and the reaction mixture was stirred and heated to 100° C. for 18 hours. After cooling to ambient temperature the reaction mixture was partitioned between methylene chloride and water. The organic layer was dried with brine and sodium sulphate, filtered and evaporated. The residual gum was triturated under diethyl ether. There was thus obtained the title compound as a solid (0.04 g, 20%); NMR: 1.05 (t, 3H), 1.4 (t, 3H), 2.13 (s, 3H), 3.35 (m, 4H), 3.51 (m, 4H), 3.7 (m, 4H), 3.95 (s, 3H), 4.91 (s, 2H), 7.11 (m, 1H), 7.18 (s, 1H), 7.24 (s, 1H), 7.29 (m, 1H), 7.6 (m, 1H), 7.77 (m, 2H), 8.26 (m, 2H), 9.3 (broad s, 1H), 10.32 (broad s, 1H); m/s: M+H+ 600.

Workup

  1. temperatureAfter cooling to ambient temperature the reaction mixture
  2. customwas partitioned between methylene chloride and water
  3. dry with materialThe organic layer was dried with brine and sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residual gum was triturated under diethyl ether

Sources & evidence

ORD record
ord-66d703534c0a4d7da9a66add5f5b04c6
Source dataset
uspto-grants-2003_07
Patent number
US06593333B1

Reaction notes

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