Acetic Acid → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({6-fluoro-3'-[(4-methyl-1-piperazinyl)methyl]-3-biphenylyl}methyl)-5-methyl-1,3-benzenedicarboxamide

HRID 564659Notes

Reaction equation

HRID 564659 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([C:30]([NH:32][CH2:33][C:34]4[CH:35]=[C:36]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH:47]=O)[CH:42]=5)[C:37]([F:40])=[CH:38][CH:39]=4)=[O:31])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH3:51][N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>CS(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([C:30]([NH:32][CH2:33][C:34]4[CH:35]=[C:36]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:55]6[CH2:56][CH2:57][N:52]([CH3:51])[CH2:53][CH2:54]6)[CH:42]=5)[C:37]([F:40])=[CH:38][CH:39]=4)=[O:31])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 2724942TriacetoxyborohydrideHCID 57813273N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-fluoro-3'-formyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamide

Product 1

HCID 57813402N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({6-fluoro-3'-[(4-methyl-1-piperazinyl)methyl]-3-biphenylyl}methyl)-5-methyl-1,3-benzenedicarboxamideYield 66.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamide (30 mg, 0.044 mmol), 1-methylpiperazine (44.4 mg, 0.44 mmol, 10 eq) and acetic acid (2.54 μL, 0.044 mmol, 1 eq) were dissolved in DMSO (1.5 mL). The mixture was stirred in VX-2500 Multi-Tube Vortexer for overnight at room temperature. MP-triacetoxyborohydride (133 mg, 0.310 mmol, 7 eq) was then added and the mixture was stirred again in VX-2500 Multi-Tube Vortexer for overnight at room temperature. The reaction mixture was filtered through a polypropylene cartridge (10 mL tube) on Bohdan Miniblock in a reaction tube and concentrated in a Glas-Col evaporator. The reaction mixture was then purified using a Gilson HPLC with a water-acetonitrile with 0.1% TFA buffer. The desired product fractions were combined, filtered through amine cartouche (500 mg) on Bohdan Miniblock and concentrated in a Glas-Col evaporator, giving 22.15 mg (59.1%) of the title compound. LC-MS m/z 761 (M+H)+, 1.38 min (ret time).

Workup

  1. filtrationThe reaction mixture was filtered through a polypropylene cartridge (10 mL tube) on Bohdan Miniblock in a reaction tube
  2. concentrationconcentrated in a Glas-Col evaporator
  3. customThe reaction mixture was then purified
  4. filtrationfiltered through amine cartouche (500 mg) on Bohdan Miniblock
  5. concentrationconcentrated in a Glas-Col evaporator

Sources & evidence

ORD record
ord-aafb60b4b0aa4322a1eaf593ee07aca9
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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