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

HRID 657437Notes

Reaction equation

HRID 657437 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18](=[O:45])[CH2:19][CH2:20][C:21]([NH:23][CH2:24][C:25]2[C:26]([NH:38][CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[C:27]3[CH:35]=[N:34][N:33]([CH2:36][CH3:37])[C:28]3=[N:29][C:30]=2[CH2:31][CH3:32])=[O:22])=[CH:4][CH:3]=1.C[C@H:47]1[CH2:52][NH:51][CH2:50][CH2:49][N:48]1C(OC(C)(C)C)=O.C(O)(=O)C>CS(C)=O>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:48]3[CH2:49][CH2:50][NH:51][CH2:52][CH2:47]3)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18](=[O:45])[CH2:19][CH2:20][C:21]([NH:23][CH2:24][C:25]2[C:26]([NH:38][CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[C:27]3[CH:35]=[N:34][N:33]([CH2:36][CH3:37])[C:28]3=[N:29][C:30]=2[CH2:31][CH3:32])=[O:22])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylateHCID 57819867N-[(6-chloro-3'-formyl-3-biphenylyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide

Product 1

HCID 57819910N-{[6-Chloro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamideYield 16.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

N-[(6-Chloro-3′-formyl-3-biphenylyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}butanediamide (37.8 mg. 0.06 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial containing 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (0.18 mmol), acetic acid (3.6 mg, 0.6 mmol) and fitted with a magnetic stir bar. 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 reversed phase HPLC using the Gilson (acidic conditions with 0.1% TFA in the solvents). The product after HPLC purification was dissolved in 3 mL of MeOH and passed through a 0.5 g amine column (washed with 8 mL of MeOH) to afford 6.92 mg of the title compound (16.4%). LC-MS m/z 701 (M+H)+, 1.19 min (ret time).

Workup

  1. customfitted with a magnetic stir bar
  2. stirringthe solution was stirred for another 12 h
  3. filtrationThe polymer reagent was filtered
  4. custompurification
  5. customThe product after HPLC purification
  6. dissolutionwas dissolved in 3 mL of MeOH
  7. washpassed through a 0.5 g amine column (washed with 8 mL of MeOH)

Sources & evidence

ORD record
ord-7ed18b9de38f4be1b05522ba13ba4523
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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