Triethylamine → 4-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-7-{2-[4-(2-dimethylaminoacetyl)piperazin-1-yl]ethoxy}-5-isopropoxyquinazoline

HRID 2374438Notes

Reaction equation

HRID 2374438 reaction equation
[Cl:1][C:2]1[C:3]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:26][CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[CH:19][C:20]=3[O:22][CH:23]([CH3:25])[CH3:24])[N:15]=[CH:14][N:13]=2)=[C:4]2[O:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1.Cl.[CH3:36][N:37]([CH3:42])[CH2:38][C:39](Cl)=[O:40].C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:26][CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][N:32]([C:39](=[O:40])[CH2:38][N:37]([CH3:42])[CH3:36])[CH2:31][CH2:30]4)=[CH:19][C:20]=3[O:22][CH:23]([CH3:25])[CH3:24])[N:15]=[CH:14][N:13]=2)=[C:4]2[O:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 10051129HCID 10051129, compoundHCID 139949912-(Dimethylamino)acetyl chloride hydrochloride2×

Product 1

HCID 100082454-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-7-{2-[4-(2-dimethylaminoacetyl)piperazin-1-yl]ethoxy}-5-isopropoxyquinazolineYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

4-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-5-isopropoxy-7-(2-piperazin-1-ylethoxy)quinazoline (0.2 g) was added to a stirred mixture of 2-dimethylaminoacetyl chloride hydrochloride (0.097 g), triethylamine (0.15 ml) and methylene chloride (5 ml) that had been cooled to 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 2 hours. A second portion of each of 2-dimethylaminoacetyl chloride hydrochloride (0.097 g) and triethylamine (0.057 ml) were added and the reaction was stirred at ambient temperature for 16 hours overnight. Methylene chloride (50 ml) was added and the reaction mixture was extracted twice with a saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with a 9:1 mixture of methylene chloride and methanol and ending with a 90:8:2 mixture of methylene chloride, methanol and a saturated methanolic ammonia solution. There was thus obtained the title compound as a foam (0.155 g); NMR Spectrum: (CDCl3) 1.55 (d, 6H), 2.3 (s, 6H), 2.6 (m, 4H), 2.9 (t, 2H), 3.1 (s, 2H), 3.65 (m, 4H), 4.25 (t, 2H), 4.85 (s, 1H), 6.15 (s, 2H), 6.55 (s, 1H), 6.85 (s, 1H), 7.75 (s, 1H), 8.6 (s, 1H), 9.6 (s, 1H); Mass Spectrum: M+H+ 572 and 574; Elemental Analysis: Found C, 55.1; H, 6.1; N, 16.8; C27H34ClN7O5 0.75H2O requires C, 55.4; H, 6.1; N, 16.7%.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringthe reaction was stirred at ambient temperature for 16 hours overnight
  3. extractionthe reaction mixture was extracted twice with a saturated aqueous sodium bicarbonate solution
  4. dry with materialThe organic phase was dried over magnesium sulphate
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica using
  7. temperatureincreasingly polar solvent mixtures
  8. additionstarting with a 9:1 mixture of methylene chloride and methanol
  9. additionending with a 90:8:2 mixture of methylene chloride, methanol

Sources & evidence

ORD record
ord-78d1008f414a4a2dbd14ecb45c66c110
Source dataset
uspto-grants-2008_12
Patent number
US07462623B2

Reaction notes

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