Ammonium Chloride → N-[(1S)-2-amino-1-phenylethyl]-methyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

HRID 44628Notes

Reaction equation

HRID 44628 reaction equation
[N:1]([CH2:4][C@@H:5]([NH:12][C:13]([C:15]1[C:19]2[CH2:20][CH2:21][C:22]3[CH:23]=[N:24][C:25]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]5)=[CH:31][CH:30]=4)=[N:26][C:27]=3[C:18]=2[N:17]([CH3:42])[N:16]=1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[N+]=[N-].[NH4+].[Cl-]>CO.O.[Fe]>[NH2:1][CH2:4][C@@H:5]([NH:12][C:13]([C:15]1[C:19]2[CH2:20][CH2:21][C:22]3[CH:23]=[N:24][C:25]([NH:28][C:29]4[CH:30]=[CH:31][C:32]([N:35]5[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]5)=[CH:33][CH:34]=4)=[N:26][C:27]=3[C:18]=2[N:17]([CH3:42])[N:16]=1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 57531684N-[(1S)-2-azido-1-phenylethyl]-1-methyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

Product 1

HCID 57531675N-[(1S)-2-amino-1-phenylethyl]-methyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideYield 76.7%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 129 mg (0.228 mmol) of N-[(1S)-2-azido-1-phenylethyl]-1-methyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide in 16 mL of methanol, 65 mg (1.2 mmol) of NH4Cl dissolved in 3.2 mL of water and 39 mg of iron (0.7 mmol) were added and the mixture refluxed overnight. The suspension was cooled to room temperature and filtered. After removal of methanol, solid Na2CO3 was added portionwise to the aqueous phase up to pH 10 and the product was then extracted with dichloromethane. Flash chromatography of the crude (eluant dichloromethane/methanol 95/5) yielded 94 mg of the title compound.

Workup

  1. temperaturethe mixture refluxed overnight
  2. filtrationfiltered
  3. customAfter removal of methanol, solid Na2CO3
  4. additionwas added portionwise to the aqueous phase up to pH 10
  5. extractionthe product was then extracted with dichloromethane

Sources & evidence

ORD record
ord-6f2ee9b1944b4353ae3aa0b18f2cd8bf
Source dataset
uspto-grants-2013_09
Patent number
US08541429B2

Reaction notes

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