Dimethylformamide → 4-Amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7,8-trimethoxyquinazoline

HRID 1448960Notes

Reaction equation

HRID 1448960 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4](Cl)[N:3]=1.[O:19]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[O:22][CH2:21][CH:20]1[C:29]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)=[O:30].C(N(CC)CC)C.CN(C)C=O>C(O)CCC.O1C2C=CC=CC=2OCC1C(N1CCNCC1)=O.CCOCC>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:16][CH3:17])[C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:34]2[CH2:35][CH2:36][N:31]([C:29]([CH:20]3[O:19][C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[O:22][CH2:21]3)=[O:30])[CH2:32][CH2:33]2)[N:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 2735449N-1,4-Benzodioxane-2-carbonyl piperazineHCID 30158042-Chloro-6,7,8-trimethoxyquinazolin-4-amine

Product 1

HCID 203513374-Amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7,8-trimethoxyquinazolineYield 32.5%

Reagents, catalysts & solvents 3

HCID 2735449N-1,4-Benzodioxane-2-carbonyl piperazineCatalystHCID 2631-ButanolSolventHCID 3283Diethyl EtherSolvent

Procedure

4-amino-2-chloro-6,7,8-trimethoxyquinazoline (1 g.) and N-(1,4-benzodioxan-2-carbonyl)piperazine (1.168 g.) were heated under reflux in n-butanol (67 ml.) with triethylamine (1.87 g.) for 24 hours. Further N-(1,4-benzodioxan-2-carbonyl)piperazine (0.026 g.) was then added and the mixture heated under reflux for an additional 30 hours. Butanol was then removed in vacuo and the residue partitioned between aqueous sodium carbonate solution and chloroform. The combined chloroform extracts were washed with water, dried (Na2SO4) and evaporated in vacuo to leave a solid (3.4 g.) which was taken up in the minimum quantity of dimethylformamide then set aside at 0° C. overnight. Ether was then added and the cloudy solution further cooled to yield 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)piperazin-1-yl]-6,7,8-trimethoxyquinazoline (0.58 g.), m.p. 269°-271° C.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for an additional 30 hours
  3. customButanol was then removed in vacuo
  4. customthe residue partitioned between aqueous sodium carbonate solution and chloroform
  5. washThe combined chloroform extracts were washed with water
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customto leave a solid (3.4 g.) which
  9. temperaturethe cloudy solution further cooled

Sources & evidence

ORD record
ord-ed7ed40688c34d1499d0c0e55402e0f1
Source dataset
uspto-grants-1980_02
Patent number
US04188390

Reaction notes

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