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

HRID 662116Notes

Reaction equation

HRID 662116 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:47][CH3:48])=[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:39]5[CH:44]=[CH:43][CH:42]=[C:41]([CH:45]=O)[CH:40]=5)[CH:36]=[CH:37][CH:38]=4)=[O:30])[N: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].[CH3:49][C@@H:50]1[CH2:55][NH:54][CH2:53][C@H:52]([CH3:56])[NH:51]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]([CH2:47][CH3:48])=[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:39]5[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:54]6[CH2:53][C@H:52]([CH3:56])[NH:51][C@H:50]([CH3:49])[CH2:55]6)[CH:40]=5)[CH:36]=[CH:37][CH:38]=4)=[O:30])[N: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 4

HCID 176Acetic AcidHCID 2724942TriacetoxyborohydrideHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 57819366N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

Product 1

HCID 44193249N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-{[(3R,5S)-3,5-dimethyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-2,6-pyridinedicarboxamideYield 27.2%

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′-[(3′-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (40 mg, 0.062 mmol), (2R,6S)-2,6-dimethylpiperazine (70.73 mg, 0.619 mmol, 10 eq) and acetic acid (3.55 μL, 0.062 mmol, 1 eq) were dissolved in DMSO (1.5 mL). The mixture was stirred in a VX-2500 Multi-Tube Vortexer overnight at room temperature. MP-triacetoxyborohydride (195 mg, 0.482 mmol, 7.78 eq) was then added and the mixture was stirred again in the VX-2500 Multi-Tube Vortexer overnight at room temperature. The reaction mixture was filtered through a polypropylene cartridge (10 mL tube) on a Bohdan Miniblock in a reaction tube and concentrated in a Glas-Col evaporator. The reaction mixture was then purified by Gilson HPLC with a water-acetonitrile with 0.1% TFA buffer. The desired product fractions were combined, filtered through amine cartouche (500 mg) on a Bohdan Miniblock and concentrated in a Glas-Col evaporator, giving 11.3 mg (27.2%) of the title compound. LC-MS m/z 744 (M+H)+, 1.41 min (ret time).

Workup

  1. filtrationThe reaction mixture was filtered through a polypropylene cartridge (10 mL tube) on a Bohdan Miniblock in a reaction tube
  2. concentrationconcentrated in a Glas-Col evaporator
  3. customThe reaction mixture was then purified by Gilson HPLC with a water-acetonitrile with 0.1% TFA buffer
  4. filtrationfiltered through amine cartouche (500 mg) on a Bohdan Miniblock
  5. concentrationconcentrated in a Glas-Col evaporator

Sources & evidence

ORD record
ord-30fcc35765f0493999109f8070907f4f
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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