Methyl chloroformate → 6-Bromo-2-(3-aminopropyl)phthalazin-1(2H)-one

HRID 622130Notes

Reaction equation

HRID 622130 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH2:14][CH2:15]C(O)=O)[N:6]=[CH:5]2.C([N:21](CC)CC)C.ClC(OC)=O.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH2:14][CH2:15][NH2:21])[N:6]=[CH:5]2

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 33557Sodium AzideHCID 142348436-Bromo-2-(3-carboxypropyl)phthalazin-1(2H)-one

Product 1

HCID 142348446-Bromo-2-(3-aminopropyl)phthalazin-1(2H)-one

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

6-Bromo-2-(3-carboxypropyl)phthalazin-1(2H)-one (9.3 gm, 0.03 mole, prepared in Example XIV) was dissolved in 185 ml acetone by adding 4.7 ml triethylamine (0.0335 mole). The slightly cloudy solution was clarified, cooled to <10° C. and 3.8 gm methyl chloroformate (0.04 mole) was added over about 5 minutes. Stirred with cooling for another 30 minutes, then added a solution of 4 gm sodium azide (0.062 mole) in 25 ml water. Stirred for 30 minutes, added to 400 ml ice water and extracted three times with 80 ml methylene dichloride. This solution was dried, 4 ml of trifluoroacetic acid was added, and the solution refluxed for 18 hours. Methanol (100 ml) was added and the solution shaken with dilute potassium carbonate solution to free the base. The resulting solution was acidified with 10 ml of 30% HBr in acetic acid, diluted with 900 ml ether, filtered and washed with ethyl acetate. The product weighed 6.3 gm and showed a single spot on tlc, Rf =0.28 (using 10% methanol in chloroform on an ammonia treated silica plate).

Workup

  1. temperaturecooled to <10° C.
  2. temperaturewith cooling for another 30 minutes
  3. stirringStirred for 30 minutes
  4. extractionextracted three times with 80 ml methylene dichloride
  5. customThis solution was dried
  6. addition4 ml of trifluoroacetic acid was added
  7. temperaturethe solution refluxed for 18 hours
  8. additionMethanol (100 ml) was added
  9. stirringthe solution shaken with dilute potassium carbonate solution
  10. additiondiluted with 900 ml ether
  11. filtrationfiltered
  12. washwashed with ethyl acetate
  13. additiontreated silica plate)

Sources & evidence

ORD record
ord-16e84f8a02724231b792d0717d610e04
Source dataset
uspto-grants-1988_09
Patent number
US04769369

Reaction notes

Loading…