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

HRID 564633Notes

Reaction equation

HRID 564633 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=O)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[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].[CH3:50][CH:51]1[CH2:56][NH:55][CH2:54][CH:53]([CH3:57])[NH:52]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CS(C)=O.[Cl-].[Cl-].[Zn+2]>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][N:55]6[CH2:54][CH:53]([CH3:57])[NH:52][CH:51]([CH3:50])[CH2:56]6)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 660562,6-DimethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 57813252N-{[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]-1,3-benzenedicarboxamide

Product 1

HCID 44180315N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({3'-[(3,5-dimethyl-1-piperazinyl)methyl]-6-fluoro-3-biphenylyl}methyl)-1,3-benzenedicarboxamideYield 51.7%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 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]-1,3-benzenedicarboxamide (50.0 mg. 0.076 mmol) was diluted in DMSO (1.0 mL) and dispensed into a 1 dram vial containing 2,6-dimethylpiperazine (0.76 mmol), ZnCl2 (0.032 mmol, 4.2 mg), NaB(OAc)3H (0.76 mmol, 180 mg), with fitted magnetic stir bar, for 12 h. Purification was completed via a Gilson HPLC and desired product collected. The product was dissolved in dichloromethane (1 mL) and washed though 2 g of SPE-Amine in a column (EtOAc:MeOH=4:1, 5 mL) to afford 29.9 mg of the title compound (51.6%). LC-MS m/z 762 (M+H)+, 1.38 min (ret time).

Workup

  1. customwith fitted magnetic stir bar
  2. customPurification
  3. customcollected
  4. dissolutionThe product was dissolved in dichloromethane (1 mL)
  5. washwashed though 2 g of SPE-Amine in a column (EtOAc:MeOH=4:1, 5 mL)

Sources & evidence

ORD record
ord-580ae770dde343f19854923fa4089992
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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