2-Methoxyethanol → Terazosin

HRID 1413792Notes

Reaction equation

HRID 1413792 reaction equation
Cl[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:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)=[O:23].COCCO>C(N(CC)CC)C>[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:27]2[CH2:28][CH2:29][N:24]([C:22]([CH:18]3[CH2:19][CH2:20][CH2:21][O:17]3)=[O:23])[CH2:25][CH2:26]2)[N:11]=1

Participants

5

Reactant 3

HCID 80192-Methoxyethanol2×HCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 27346411-(Tetrahydro-2-furoyl)piperazine

Product 1

HCID 5401TerazosinYield 86.6%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Sixty grams (0.25 M) of 2-chloro-4-amino-6,7-dimethoxyquinazoline and 56.8 grams (0.308 M) of N-(2-tetrahydrofuroyl)piperazine were added to a stirred solution of 500 grams of Methyl Cellosolve® (ethylene glycol monomethyl ether) and 37.9 grams of triethylamine. The reaction mixture was heated to and maintained at a temperature of between 115° to 120° C. for 8 hours, and then allowed to cool to room temperature overnight. The Methyl Cellosolve® ether was removed by vacuum distillation, the residue was taken up in 1920 ml of 45° C. filtered water, and the temperature of the solution was readjusted to 45° C. The pH was then adjusted to pH 2.5 with concentrated hydrochloric acid and the solution was mixed for 1 hour. The solution was then filtered and the pH adjusted to pH 8.3 with filtered ammonia water (28%). After heating for 1 hour at 65° C., the solution was cooled to 15° C. and held at a temperature of between 15°-20° C. for 16 hours. The resulting crystalline product was filtered, washed with cold water (15° C.) and dried in vacuo at 65° C. to yield 84 grams of anhydrous base.

Workup

  1. temperatureThe reaction mixture was heated to and
  2. temperaturemaintained at a temperature of between 115° to 120° C. for 8 hours
  3. customThe Methyl Cellosolve® ether was removed by vacuum distillation
  4. customwas taken up in 1920 ml of 45° C.
  5. filtrationfiltered water
  6. customwas readjusted to 45° C
  7. additionthe solution was mixed for 1 hour
  8. filtrationThe solution was then filtered
  9. temperatureAfter heating for 1 hour at 65° C.
  10. temperaturethe solution was cooled to 15° C.
  11. filtrationThe resulting crystalline product was filtered
  12. washwashed with cold water (15° C.)
  13. customdried in vacuo at 65° C.

Sources & evidence

ORD record
ord-58f52f00d3ab4346b7fcb79cecf1678f
Source dataset
uspto-grants-1981_02
Patent number
US04251532

Reaction notes

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