Triethylamine → 6,7-dimethoxy-1-[4-(N-methyltrifluoracetamido)piperidino]phthalazine

HRID 1577833Notes

Reaction equation

HRID 1577833 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[N:4][N:3]=1.Cl.[NH:17]1[CH2:22][CH2:21][CH:20]([N:23]([CH3:30])[C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH2:19][CH2:18]1.C(N(CC)CC)C>C(O)CC(C)C>[CH3:15][O:14][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][C:9]=1[O:12][CH3:13])[C:2]([N:17]1[CH2:22][CH2:21][CH:20]([N:23]([CH3:30])[C:24](=[O:29])[C:25]([F:27])([F:26])[F:28])[CH2:19][CH2:18]1)=[N:3][N:4]=[CH:5]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 205111771-Chloro-6,7-dimethoxyphthalazineHCID 20569886N-(piperid-4-yl)-N-methyltrifluoracetamide hydrochloride

Product 1

HCID 205699366,7-dimethoxy-1-[4-(N-methyltrifluoracetamido)piperidino]phthalazineYield 36.3%

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

1-Chloro-6,7-dimethoxyphthalazine (4.5 g), N-(piperid-4-yl)-N-methyltrifluoracetamide hydrochloride (9.9 g) and triethylamine (5.5 ml) were heated together for 5 hours at 100° in iso-amylalcohol (100 ml). The solution was cooled to room temperature and the excess iso-amylalcohol was removed by distillation in vacuo. The residue was dissolved in dilute hydrochloric acid to pH 2, extracted with chloroform (2×100 ml), the chloroform extract shaken with dilute sodium hydroxide, and then quickly separated. The organic phase was washed with water (150 ml), dried over magnesium sulphate, and taken to dryness in vacuo. The resultant brown oil was triturated with ether, filtered, and the filtrate was left standing at room temperature for two hours, during which time a yellow solid precipitated from solution. This solid was collected and crystallized from iso-propylalcohol, yielding 6,7-dimethoxy-1-[4-(N-methyltrifluoracetamido)piperidino]phthalazine (2.9 g), m.p. 150°-152°.

Workup

  1. customthe excess iso-amylalcohol was removed by distillation in vacuo
  2. dissolutionThe residue was dissolved in dilute hydrochloric acid to pH 2
  3. extractionextracted with chloroform (2×100 ml)
  4. extractionthe chloroform extract
  5. customquickly separated
  6. washThe organic phase was washed with water (150 ml)
  7. dry with materialdried over magnesium sulphate
  8. customThe resultant brown oil was triturated with ether
  9. filtrationfiltered
  10. waitthe filtrate was left
  11. customa yellow solid precipitated from solution
  12. customThis solid was collected
  13. customcrystallized from iso-propylalcohol

Sources & evidence

ORD record
ord-c36d29766db34ae89a105f86156bb5c9
Source dataset
uspto-grants-1981_09
Patent number
US04289772

Reaction notes

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