N-methyl-2-pyrrolidone → 4-(3-Chloro-4-methoxybenzyl)amino-6-cyano-1-(4-cyanopiperidino)phthalazine hydrochloride

HRID 47332

Reaction equation

HRID 47332 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]#[N:9])[CH2:4][CH2:3]1.[Cl:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([C:21]#[N:22])=[CH:18][CH:19]=2)[C:14]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([Cl:33])[CH:26]=2)=[N:13][N:12]=1.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>C(OCC)(=O)C>[ClH:10].[Cl:33][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=1[O:31][CH3:32])[CH2:24][NH:23][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[C:17]([C:21]#[N:22])[CH:16]=2)[C:11]([N:2]2[CH2:7][CH2:6][CH:5]([C:8]#[N:9])[CH2:4][CH2:3]2)=[N:12][N:13]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 104510651-Chloro-4-((3-chloro-4-methoxybenzyl)amino)-6-phthalazinecarbonitrileHCID 227446374-Piperidinecarbonitrile hydrochloride

Product 1

HCID 227445544-(3-Chloro-4-methoxybenzyl)amino-6-cyano-1-(4-cyanopiperidino)phthalazine hydrochlorideYield 67.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of 1.2 g of the resulting 4-piperidinecarbonitrile hydrochloride, 1.0 g 1-chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine, 1.8 g diisopropylethylamine, and 10 ml 1-methyl-2-pyrrolidone was stirred at 170° C. for 2 hr and 30 min. After cooling, ethyl acetate was added to the reaction solution which was then washed with water and brine. After it was dried over anhydrous sodium sulfate, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography. The resulting free compound was dissolved in ethyl acetate, then a solution of 4 N hydrochloric acid/ethyl acetate was added thereto, and the resulting crystals were collected by filtration to give 880 mg of the title compound as a yellow powder.

Workup

  1. temperatureAfter cooling
  2. washwas then washed with water and brine
  3. dry with materialAfter it was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated
  5. customthe resulting residue was purified by silica gel column chromatography
  6. dissolutionThe resulting free compound was dissolved in ethyl acetate
  7. additiona solution of 4 N hydrochloric acid/ethyl acetate was added
  8. filtrationthe resulting crystals were collected by filtration

Sources & evidence

ORD record
ord-7679366578cc4903857d63e6485b8519
Source dataset
uspto-grants-2004_03
Patent number
US06699870B2

Linked notes

Loading…