Methane → Doxazosin

HRID 1969339Notes

Reaction equation

HRID 1969339 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[C:11]([OH:13])=O.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH3:27])[N:22]=[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[N:20]=[C:19]2[NH2:34].C1(N=C=NC2CCCCC2)CCCCC1.C>CC(C)=O.O1CCCC1>[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:19]([NH2:34])=[N:20][C:21]([N:28]3[CH2:29][CH2:30][N:31]([C:11]([CH:2]4[O:1][C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3]4)=[O:13])[CH2:32][CH2:33]3)=[N:22][C:23]2=[CH:24][C:25]=1[O:26][CH3:27]

Participants

7

Reactant 4

HCID 297MethaneHCID 10868DicyclohexylcarbodiimideHCID 6162672-(1-Piperazinyl)-4-amino-6,7-dimethoxyquinazolineHCID 27354501,4-Benzodioxane-2-carboxylic acid

Product 1

HCID 3157DoxazosinYield 93.6%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

In a reaction vessel, 0.25 mol (45.0 g) of 2,3-dihydro-1,4-benzodioxine-2-carboxylic acid, tetrahydrofuran (328 ml) and 6,7-dimethoxy-2-(piperazin-1-yl)quinazolin-4-amine (0.22 mol; 63.58 g) were charged and contents were stirred at 20-25° C. for 5-10 min. To the resulting mixture dicyclohexylcarbodiimide (0.26 mol; 54.0 g) was added and stirring continued at 20-25° C. for 1.5 hr. To the resulting reaction mass charcoal was added and contents were stirred at 26-28° C. for 45 min. The contents were filtered through celite and washed with tetrahydrofuran. The solvent was distilled out at 35° C. under reduced pressure to obtain solid residue. Acetone (1000 ml) was added to the solid and contents were refluxed for 2 hr. On cooling to 25-28° C., the slurry was filtered, washed with acetone and dried at 60° C. under reduced pressure to obtain 93 g of doxazosin base (HPLC purity −99.0%).

Workup

  1. stirringstirring
  2. waitcontinued at 20-25° C. for 1.5 hr
  3. additionwas added
  4. stirringcontents were stirred at 26-28° C. for 45 min
  5. filtrationThe contents were filtered through celite
  6. washwashed with tetrahydrofuran
  7. distillationThe solvent was distilled out at 35° C. under reduced pressure
  8. customto obtain solid residue
  9. temperaturewere refluxed for 2 hr
  10. temperatureOn cooling to 25-28° C.
  11. filtrationthe slurry was filtered
  12. washwashed with acetone
  13. customdried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-f2a28d2768a34f649b7368d7d42ed0c1
Source dataset
uspto-grants-2013_04
Patent number
US08426590B2

Reaction notes

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