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}propanediamide

HRID 657435Notes

Reaction equation

HRID 657435 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:44])[CH2:19][C:20]([NH:22][CH2:23][C:24]2[C:25]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:26]3[CH:34]=[N:33][N:32]([CH2:35][CH3:36])[C:27]3=[N:28][C:29]=2[CH2:30][CH3:31])=[O:21])=[CH:4][CH:3]=1.[NH:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1.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:45]3[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18](=[O:44])[CH2:19][C:20]([NH:22][CH2:23][C:24]2[C:25]([NH:37][CH:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[C:26]3[CH:34]=[N:33][N:32]([CH2:35][CH3:36])[C:27]3=[N:28][C:29]=2[CH2:30][CH3:31])=[O:21])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4837PiperazineHCID 57819914N-[(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}propanediamide

Product 1

HCID 57819931N-{[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}propanediamideYield 29.3%

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}propanediamide (37.0 mg, 0.06 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial containing piperazine (0.18 mmol) and acetic acid (3.6 mg, 0.6 mmol) and fitted with a magnetic stir bar. The resulting solution was stirring 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 off and purification was completed using reversed phase HPLC (acidic conditions) via a Gilson. The product after HPLC purification was dissolved in 3 mL of MeOH and was passed through a 0.5 g amine column (washed with 8 mL of MeOH) to afford 12.1 mg of the title compound (29.3%). LC-MS m/z 687 (M+H)+, 1.88 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 off
  4. custompurification
  5. customThe product after HPLC purification
  6. dissolutionwas dissolved in 3 mL of MeOH
  7. washwas passed through a 0.5 g amine column (washed with 8 mL of MeOH)

Sources & evidence

ORD record
ord-1d4fdbd30cd84fb7acd7f409a62e5331
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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