Ammonia → 1-(3-Amino-3-methyl-1-butynyl)-4-[(3-chloro-4-methoxybenzyl)amino]-6-phthalazinecarbonitrile hydrochloride

HRID 2300183Notes

Reaction equation

HRID 2300183 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([C:19]#[N:20])=[CH:16][CH:17]=2)[C:12]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([Cl:31])[CH:24]=2)=[N:11][N:10]=1.[NH2:32][C:33]([CH3:37])([CH3:36])[C:34]#[CH:35].N>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C.CN(C)C=O>[ClH:8].[NH2:32][C:33]([CH3:37])([CH3:36])[C:34]#[C:35][C:9]1[C:18]2[C:13](=[CH:14][C:15]([C:19]#[N:20])=[CH:16][CH:17]=2)[C:12]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([Cl:31])[CH:24]=2)=[N:11][N:10]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 763193-Butyn-2-amine, 2-methyl-HCID 104510651-Chloro-4-((3-chloro-4-methoxybenzyl)amino)-6-phthalazinecarbonitrile

Product 1

HCID 227444991-(3-Amino-3-methyl-1-butynyl)-4-[(3-chloro-4-methoxybenzyl)amino]-6-phthalazinecarbonitrile hydrochlorideYield 72.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

0.39 ml triethylamine was added to a mixture of 500 mg 1-chloro-4-[(3-chloro-4-methoxybenzyl)amino]-6-phthalazine carbonitrile, 53 mg cuprous iodide, 98 mg dichlorobis(triphenylphosphine)palladium (II), 347 mg 3-amino-3-methyl-1-butyne, and 10 ml dimethylformamide, and the mixture was stirred at 80° C. for 3 hr in a nitrogen atmosphere. After cooling, ethyl acetate was added to the reaction solution, then water and conc. aqueous ammonia were added thereto, and the organic layer was recovered. The organic layer was washed with dilute aqueous ammonia and brine, and dried over anhydrous sodium sulfate. It was filtered and the filtrate was evaporated. The resulting residue was purified by NH-form silica gel column chromatography to give 446 mg of the title compound. The product was converted in a usual manner into the hydrochloride.

Workup

  1. temperatureAfter cooling
  2. customthe organic layer was recovered
  3. washThe organic layer was washed with dilute aqueous ammonia and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationIt was filtered
  6. customthe filtrate was evaporated
  7. customThe resulting residue was purified by NH-form silica gel column chromatography

Sources & evidence

ORD record
ord-b39ff1413e314b9d855f0ee6de25d76d
Source dataset
uspto-grants-2002_12
Patent number
US06498159B1

Reaction notes

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