Hydrazine hydrate (1:1) → 3-[[4-[2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazinyl]ethoxy]phenyl]oxy]propanamine trihydrochloride

HRID 2418008Notes

Reaction equation

HRID 2418008 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][CH2:37][N:38]5C(=O)C6=CC=CC=C6C5=O)=[CH:30][CH:29]=4)[CH2:21][CH2:20]3)[C:4]=2[CH:3]=1.O.NN>C(O)C>[ClH:1].[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][O:27][C:28]4[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][CH2:37][NH2:38])=[CH:32][CH:33]=4)[CH2:23][CH2:24]3)[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 133384601-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-[2-[4-(3-phthalimidopropyloxy)phenoxy]ethyl]piperazine

Product 1

HCID 133384633-[[4-[2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazinyl]ethoxy]phenyl]oxy]propanamine trihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 500 ml of ethanol containing 1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-4-[2-[4-(3-phthalimidopropyloxy)phenoxy]ethyl]piperazine (10.5 g) was added 85% hydrazine hydrate (2.95 g). The solution was stirred and refluxed for 24 hours. The insoluble phthalazinedione was then removed by filtration and the filtrate concentrated in vacuo. Water (200 ml) and concentrated ammonium hydroxide (50 ml) was added to the residue. The oil was extracted with dichloromethane and the solution dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue dissolved in ethyl acetate. Hydrogen chloride was bubbled into the solution to precipitate the product as its trihydrochloride salt which was recovered by filtration and crystallized from acetonitrile-methanol. The yield of 3-[[4-[2-[4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-piperazinyl]ethoxy]phenyl]oxy]propanamine trihydrochloride, mp 237°-240°, was 6.0 g.

Workup

  1. temperaturerefluxed for 24 hours
  2. customThe insoluble phthalazinedione was then removed by filtration
  3. concentrationthe filtrate concentrated in vacuo
  4. additionWater (200 ml) and concentrated ammonium hydroxide (50 ml) was added to the residue
  5. extractionThe oil was extracted with dichloromethane
  6. dry with materialthe solution dried over anhydrous sodium sulfate
  7. customThe solvent was removed in vacuo
  8. dissolutionthe residue dissolved in ethyl acetate
  9. customHydrogen chloride was bubbled into the solution
  10. customto precipitate the product as its trihydrochloride salt which
  11. filtrationwas recovered by filtration
  12. customcrystallized from acetonitrile-methanol

Sources & evidence

ORD record
ord-7ca94ab39fd342109d43300de0a7f55d
Source dataset
uspto-grants-1984_09
Patent number
US04471116

Reaction notes

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