Triethylamine → HCID 20220980, compound

HRID 980829Notes

Reaction equation

HRID 980829 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]([NH2:12])[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.O.[ClH:18].Cl.[O:20]=[C:21]1[CH2:26][C:25]([CH3:28])([CH3:27])[CH2:24][C:23]([N:29]2[CH2:35][CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:22]1.C(N(CC)CC)C>C(O)CC(C)C>[ClH:1].[ClH:18].[NH2:12][C:10]1[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=[C:2]([N:32]2[CH2:33][CH2:34][CH2:35][N:29]([C:23]3[CH2:24][C:25]([CH3:27])([CH3:28])[CH2:26][C:21](=[O:20])[CH:22]=3)[CH2:30][CH2:31]2)[N:11]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 20220989HCID 20220989, compound

Product 1

HCID 20220980HCID 20220980, compound

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

A mixture of 1.7 g (0.007 mol) of 2-chloro-4-amino-6,7-dimethoxyquinazoline, 2.2 g (0.007 mol) of (3-oxo-5,5-dimethyl-1-cyclohexen-1-yl)-homopiperazine dihydrochloride monohydrate, 3.55 g (0.035 mol) of triethylamine and 30 ml of anhydrous isoamyl alcohol is heated at the boiling point under reflux for 10 hours. After cooling, the triethylamine hydrochloride is filtered off with suction and washed with isoamyl alcohol. The alcohol phases are concentrated at 50° C. in vacuo and the residue which remains is dissolved in 200 ml of chloroform. After washing twice with water, the chloroform solution is dried with sodium sulphate and evaporated to dryness. The residue can be taken up in 20 ml of absolute ethanol. Hydrogen chloride, dissolved in ethyl alcohol, is added to this solution, followed by absolute ether, while cooling with ice, until the onset of turbidity. The 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-(3-oxo-5,5-dimethyl-1-cyclo-hexen-1-yl)-homopiperazine dihydrochloride which precipitates is filtered off with suction and washed with absolute ether. Yield: 2.1 g (60%) of melting point 259°-261° C. (decomposition). A sample recrystallised from ethanol/methanol (2:1) has a melting point of 260°-261° C. (decomposition).

Workup

  1. temperatureis heated at the boiling point
  2. temperatureunder reflux for 10 hours
  3. temperatureAfter cooling
  4. filtrationthe triethylamine hydrochloride is filtered off with suction
  5. washwashed with isoamyl alcohol
  6. concentrationThe alcohol phases are concentrated at 50° C. in vacuo
  7. dissolutionthe residue which remains is dissolved in 200 ml of chloroform
  8. washAfter washing twice with water
  9. dry with materialthe chloroform solution is dried with sodium sulphate
  10. customevaporated to dryness
  11. dissolutionHydrogen chloride, dissolved in ethyl alcohol
  12. additionis added to this solution
  13. temperaturewhile cooling with ice, until the onset of turbidity
  14. customThe 1-(4-amino-6,7-dimethoxyquinazolin-2-yl)-4-(3-oxo-5,5-dimethyl-1-cyclo-hexen-1-yl)-homopiperazine dihydrochloride which precipitates
  15. filtrationis filtered off with suction
  16. washwashed with absolute ether
  17. customA sample recrystallised from ethanol/methanol (2:1)

Sources & evidence

ORD record
ord-ff64756312d14d3f930e37d8f6f97f70
Source dataset
uspto-grants-1987_01
Patent number
US04639453

Reaction notes

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