2-Chloro-6,7-dimethoxy-4-quinazolinamine → 4-Amino-6,7-dimethoxy-2-[4-(2-phenoxypyrimidin-4-yl) piperazino]quinazoline

HRID 1903081Notes

Reaction equation

HRID 1903081 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4](Cl)[N:3]=1.Cl.Cl.[O:19]([C:26]1[N:31]=[C:30]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:29]=[CH:28][N:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O)CCC>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:35]2[CH2:36][CH2:37][N:32]([C:30]3[CH:29]=[CH:28][N:27]=[C:26]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:31]=3)[CH2:33][CH2:34]2)[N:3]=1

Participants

4

Reactant 2

HCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 138695642-Phenoxy-4-piperazinopyrimidine dihydrochloride

Product 1

HCID 138695534-Amino-6,7-dimethoxy-2-[4-(2-phenoxypyrimidin-4-yl) piperazino]quinazolineYield 9.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

4-Amino-2-chloro-6,7-dimethoxyquinazoline (0.8 g, 3.3 mmole) and 2-phenoxy-4-piperazinopyrimidine dihydrochloride (1.2 g, 3.6 mmole) were heated under reflux in n-butanol (50 ml) overnight. The mixture was then evaporated in vacuo and the residue partitioned between chloroform/methanol/saturated aqueous sodium carbonate solution (300 ml:100 ml:50 ml). The chloroform/methanol layer was separated, dried (Na2SO4), evaporated in vacuo then the residue (1 g) chromatographed on silica gel (85 g). The column was eluted with chloroform, then chloroform containing 2.5% methanol by volume, appropriate fractions combined, evaporated in vacuo and the residue recrystallized from ethanol to give the title compound, (0.14 g) m.p. 253°-254° C.

Workup

  1. customThe mixture was then evaporated in vacuo
  2. customthe residue partitioned between chloroform/methanol/saturated aqueous sodium carbonate solution (300 ml:100 ml:50 ml)
  3. customThe chloroform/methanol layer was separated
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customthe residue (1 g) chromatographed on silica gel (85 g)
  7. washThe column was eluted with chloroform
  8. customevaporated in vacuo
  9. customthe residue recrystallized from ethanol

Sources & evidence

ORD record
ord-be8298676bc54f5abc07ad440b52294f
Source dataset
uspto-grants-1984_03
Patent number
US04435401

Reaction notes

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