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

HRID 662132Notes

Reaction equation

HRID 662132 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]([CH3:39])=[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].[CH3:50][C@@H:51]1[NH:56][CH2:55][CH2:54][N:53](C(OC(C)(C)C)=O)[CH2:52]1.C(O)(=O)C>CS(C)=O>[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:56]6[CH2:55][CH2:54][NH:53][CH2:52][C@@H:51]6[CH3:50])[CH:41]=5)[C:36]([CH3:39])=[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

5

Reactant 3

HCID 176Acetic AcidHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 57819380N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

Product 1

HCID 57819401N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-methyl-3'-{[(2S)-2-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-2,6-pyridinedicarboxamideYield 33.03%

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-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (39.0 mg. 0.059 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial containing 1,1-dimethylethyl (3S)-3-methyl-1-piperazinecarboxylate (0.177 mmol, 3.0 eq) and acetic acid (3.55 mg, 0.059 mmol) and fitted magnetic stir bar. The result solution was stirring at room temperature for 4 h. MP-B(OAc)3H (0.591 mmol, 138 mg, 10.0 eq) was added and the solution was stirred for another 12 h. The polymer reagent was filtered off and MeOH (2.0 mL) and 1 drop of concentrated HCl was added to the solution. The solution was heated at 60° C.° for 12 h. Purification was completed via a Gilson HPLC (acidic conditions). The product was dissolved in 3 mL of MeOH and passed through 0.5 g amine columns (washed with 8 mL MeOH) to afford 14.5 mg (33.03%) of the title compound. LC-MS m/z 744 (M+H)+, 1.43 min (ret time).

Workup

  1. customfitted magnetic stir bar
  2. stirringthe solution was stirred for another 12 h
  3. filtrationThe polymer reagent was filtered off
  4. additionMeOH (2.0 mL) and 1 drop of concentrated HCl was added to the solution
  5. temperatureThe solution was heated at 60° C.° for 12 h
  6. customPurification
  7. dissolutionThe product was dissolved in 3 mL of MeOH
  8. washpassed through 0.5 g amine columns (washed with 8 mL MeOH)

Sources & evidence

ORD record
ord-940cb231816a47af99e50f8927544fb4
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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