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)pentanediamide

HRID 657433Notes

Reaction equation

HRID 657433 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:45][CH3:46])=[C:10]([CH2:19][NH:20][C:21](=[O:44])[CH2:22][CH2:23][CH2:24][C:25]([NH:27][CH2:28][C:29]3[CH:30]=[C:31]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([CH:42]=O)[CH:37]=4)[C:32]([F:35])=[CH:33][CH:34]=3)=[O:26])[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].[CH3:47][CH:48]1[CH2:53][NH:52][CH2:51][CH:50]([CH3:54])[NH:49]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]([CH2:45][CH3:46])=[C:10]([CH2:19][NH:20][C:21](=[O:44])[CH2:22][CH2:23][CH2:24][C:25]([NH:27][CH2:28][C:29]3[CH:30]=[C:31]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][N:52]5[CH2:51][CH:50]([CH3:54])[NH:49][CH:48]([CH3:47])[CH2:53]5)[CH:37]=4)[C:32]([F:35])=[CH:33][CH:34]=3)=[O:26])[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 57819891N-{[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]pentanediamide

Product 1

HCID 44241744N-{[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)pentanediamide

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]pentanediamide (47.0 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) and fitted with a magnetic stir bar, for 12 h. The material was purified via reverse phase HPLC using a Gilson and the desired product collected. The desired product was dissolved in dichloromethane (1 mL) and washed through 2 g SPE-amine columns (EtOAc:MeOH=4:1, 5 mL) to afford the title compound. LC-MS m/z 727 (M+H)+, 1.09 min (ret time).

Workup

  1. customfitted with a magnetic stir bar, for 12 h
  2. customThe material was purified via reverse phase HPLC
  3. customthe desired product collected
  4. dissolutionThe desired product was dissolved in dichloromethane (1 mL)
  5. washwashed through 2 g SPE-amine columns (EtOAc:MeOH=4:1, 5 mL)

Sources & evidence

ORD record
ord-395debcedfcf441faaf0508e985f71c2
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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