2-(1-Piperazinyl)-4-amino-6,7-dimethoxyquinazoline → 4-Amino-2-[4-(chroman-2-carbonyl)piperazino]-6,7-dimethoxyquinazoline

HRID 1277922Notes

Reaction equation

HRID 1277922 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH:2]1[C:11](Cl)=[O:12].[NH2:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[C:17]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[N:16]=1>C(Cl)Cl>[NH2:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[C:17]([N:29]2[CH2:34][CH2:33][N:32]([C:11]([CH:2]3[CH2:3][CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[O:1]3)=[O:12])[CH2:31][CH2:30]2)[N:16]=1

Participants

4

Reactant 2

HCID 6162672-(1-Piperazinyl)-4-amino-6,7-dimethoxyquinazolineHCID 27945832-Chromanecarbonyl chloride

Product 1

HCID 234524854-Amino-2-[4-(chroman-2-carbonyl)piperazino]-6,7-dimethoxyquinazolineYield 29.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution consisting of chroman-2-carbonyl chloride (1.13 g.) in dry methylene chloride (20 ml.) was added dropwise to a stirred suspension of 4-amino-6,7-dimethoxy-2-piperazinoquinazoline (1.38 g.) in dry methylene chloride (30 ml.) with ice bath cooling. The resulting reaction mixture was then stirred at room temperature (20° C.) overnight (approximately 16 hours), and the solid product so obtained was subsequently partitioned between aqueous sodium carbonate solution (30 ml., 1.0 N) and chloroform (220 ml.). The chloroform layer which separated was subsequently evaporated in vacuo and the resulting residue (2.5 g.) was thereafter chromatographed on silica gel (100 g.), eluting first with chloroform (200 ml.) and then with chloroform-methanol (800 ml., 97.5:2.5 parts by volume). The appropriate fractions were then collected and subsequently combined and evaporated in vacuo, and the resulting final product thereafter recrystallized from ethyl acetate to give pure 4-amino-2-[4-(chroman-2-carbonyl)piperazino]-6,7-dimethoxyquinazoline (yield, 625 mg.), m.p. 165°-167° C.

Workup

  1. temperaturecooling
  2. customThe resulting reaction mixture
  3. customthe solid product so obtained
  4. customwas subsequently partitioned between aqueous sodium carbonate solution (30 ml., 1.0 N) and chloroform (220 ml.)
  5. customThe chloroform layer which separated
  6. customwas subsequently evaporated in vacuo
  7. customthe resulting residue (2.5 g.) was thereafter chromatographed on silica gel (100 g.)
  8. washeluting first with chloroform (200 ml.)
  9. customThe appropriate fractions were then collected
  10. customevaporated in vacuo
  11. customthe resulting final product thereafter recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-653c096103e846ceb945c2120883fdd5
Source dataset
uspto-grants-1981_07
Patent number
US04279910

Reaction notes

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