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

HRID 564661Notes

Reaction equation

HRID 564661 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:50][CH3:51])=[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:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH:48]=O)[CH:43]=5)[C:37]([O:40][CH3:41])=[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].[NH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(O)(=O)C>CS(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:50][CH3:51])=[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:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:52]6[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]6)[CH:43]=5)[C:37]([O:40][CH3:41])=[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

5

Reactant 3

HCID 176Acetic AcidHCID 4837PiperazineHCID 57813428N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[3'-formyl-6-(methyloxy)-3-biphenylyl]methyl}-5-methyl-1,3-benzenedicarboxamide

Product 1

HCID 57813334N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-5-methyl-N'-{[6-(methyloxy)-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamideYield 65.4%

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-(methyloxy)-3-biphenylyl]methyl}-5-methyl-1,3-benzenedicarboxamide (40.1 mg. 0.06 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial, with fitted magnetic stir bar, containing piperazine (0.18 mmol), and acetic acid (3.6 mg, 0.6 mmol). The resulting solution was stirred at room temperature for 4 h. MP-B(OAc)3H (0.6 mmol, 140 mg) was added and the solution was stirred for another 12 h. The polymer reagent was filtered and purification was completed via Gilson HPLC (with 0.1% TFA in the solvents). The product was dissolved in 3 mL of MeOH and passed through 0.5 g amine columns (washed with 8 mL MeOH) to afford 29.8 mg (65.3%) of the title compound. LC-MS m/z 760 (M+H)+, 1.224 min (ret time).

Workup

  1. customwith fitted magnetic stir bar
  2. stirringthe solution was stirred for another 12 h
  3. filtrationThe polymer reagent was filtered
  4. custompurification
  5. dissolutionThe product was dissolved in 3 mL of MeOH
  6. washpassed through 0.5 g amine columns (washed with 8 mL MeOH)

Sources & evidence

ORD record
ord-a17cae2d35b64eb68b128a7215fb950d
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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