N,N-Dimethylglycine → 4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-7-[N-(2-dimethylaminoacetyl)piperidin-4-ylmethoxy]-6-methoxyquinazoline

HRID 2374441Notes

Reaction equation

HRID 2374441 reaction equation
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[C:12]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH2:34][CH:35]4[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:13]2[O:19][CH2:18][O:17][C:14]2=[N:15][CH:16]=1.[CH3:41][N:42]([CH3:47])[CH2:43][C:44](O)=[O:45].CN(C=O)C>C(OCC)(=O)C>[Cl:10][C:11]1[C:12]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH2:34][CH:35]4[CH2:40][CH2:39][N:38]([C:44](=[O:45])[CH2:43][N:42]([CH3:47])[CH3:41])[CH2:37][CH2:36]4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:13]2[O:19][CH2:18][O:17][C:14]2=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 685414644(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline

Product 1

HCID 685466874-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-7-[N-(2-dimethylaminoacetyl)piperidin-4-ylmethoxy]-6-methoxyquinazolineYield 28.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylethylamine (0.118 ml) was added to a mixture of 4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (0.15 g), N,N-dimethylglycine (0.042 g), 2-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate(V) (0.154 g) and DMF (3 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The mixture was diluted with ethyl acetate and washed with brine. The organic solution was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 100:3 mixture of methylene chloride and a 7M methanolic ammonia solution as eluent. There was thus obtained the title compound as a solid (0.051 g); NMR Spectrum: (DMSOd6) 1.11-1.36 (m, 2H), 1.83 (d, 2H), 2.11 (m, 1H), 2.19 (s, 6H), 2.61 (t, 1H), 3.03 (m, 2H), 3.12 (d, 1H), 3.93 (s, 3H), 4.06 (m, 3H), 4.4 (d, 1H), 6.19 (br s, 2H), 7.19 (brs, 1H), 7.78 (m, 2H), 8.39 (br s, 1H), 9.71 (br s, 1H); Mass Spectrum: M+H+ 529 and 531.

Workup

  1. washwashed with brine
  2. dry with materialThe organic solution was dried over magnesium sulphate
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica using
  5. additiona 100:3 mixture of methylene chloride

Sources & evidence

ORD record
ord-2a41006cdc67403c8bd59cc6a02ef02a
Source dataset
uspto-grants-2008_12
Patent number
US07462623B2

Reaction notes

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