Water → 5-(3,5-difluorophenylthio)-N-(4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzyl)-1H-pyrazolo[3,4-b]pyridin-3-amine

HRID 334442Notes

Reaction equation

HRID 334442 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[CH:11]=[C:12]3[C:18]([NH:19][C:20](=O)[C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[CH:23][C:22]=4[NH:34][CH:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)=[N:17][NH:16][C:13]3=[N:14][CH:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[CH:11]=[C:12]3[C:18]([NH:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[CH:23][C:22]=4[NH:34][CH:35]4[CH2:36][CH2:37][O:38][CH2:39][CH2:40]4)=[N:17][NH:16][C:13]3=[N:14][CH:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 178480684HCID 178480684, compound

Product 1

HCID 601431795-(3,5-difluorophenylthio)-N-(4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzyl)-1H-pyrazolo[3,4-b]pyridin-3-amineYield 17.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

100 mg (0.173 mmol) of N-(5-(3,5-difluorophenylthio)-1-H-pyrazolo[3,4-b]pyridine-3-yl)-4-(4-methylpiperazine-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide is added, in small fractions, to a solution of 19.64 mg (0.518 mmol) of LiAlH4 in 3 ml of anhydrous tetrahydrofuran under argon at 0° C. The reaction mixture is heated at 90° C. for 15 hours. An additional portion of 20 mg of LiAlH4 is then added and the reaction medium stirred at 90° C. for 5 hours. 45 μl of water at 0° C. is then added to the reaction mixture, followed by 45 μl of sodium hydroxide (15% wt) and finally 120 μl of water. The reaction mixture is stirred at 25° C. for 1 hour and then filtered on Dicalite. After evaporation of the solvents, the crude product is purified by chromatography. 16.80 mg (17%) of 5-(3,5-difluorophenylthio)-N-(4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzyl)-1H-pyrazolo[3,4-b]pyridin-3-amine in the form of a yellow solid is obtained.

Workup

  1. stirringThe reaction mixture is stirred at 25° C. for 1 hour
  2. filtrationfiltered on Dicalite
  3. customAfter evaporation of the solvents
  4. customthe crude product is purified by chromatography

Sources & evidence

ORD record
ord-04cadaf251f54a96a5a017bc79625c23
Source dataset
uspto-grants-2014_11
Patent number
US08883821B2

Reaction notes

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