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

HRID 657434Notes

Reaction equation

HRID 657434 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:43][CH3:44])=[C:10]([CH2:19][NH:20][C:21](=[O:42])[CH2:22][C:23]([NH:25][CH2:26][C:27]3[CH:28]=[C:29]([C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([CH:40]=O)[CH:35]=4)[C:30]([F:33])=[CH:31][CH:32]=3)=[O:24])[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].[CH3:45][C@H:46]1[CH2:51][NH:50][CH2:49][CH2:48][N:47]1C(OC(C)(C)C)=O.C(O)(=O)C>CS(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:43][CH3:44])=[C:10]([CH2:19][NH:20][C:21](=[O:42])[CH2:22][C:23]([NH:25][CH2:26][C:27]3[CH:28]=[C:29]([C:34]4[CH:35]=[CH:36][CH:40]=[C:38]([CH2:37][N:50]5[CH2:49][CH2:48][NH:47][C@@H:46]([CH3:45])[CH2:51]5)[CH:39]=4)[C:30]([F:33])=[CH:31][CH:32]=3)=[O:24])[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 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylateHCID 57819896N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-fluoro-3'-formyl-3-biphenylyl)methyl]propanediamide

Product 1

HCID 44155147N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]propanediamideYield 39.7%

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′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]propanediamide (36.0 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) and 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 to the filtrate was added MeOH (2.0 mL) and 1 drop of concentrated HCl. The solution was heated at 60° C. for 12 h. Purification was completed via reverse phase HPLC (acidic conditions) using a Gilson. The product was dissolved in 3 mL MeOH and went through a 0.5 g amine column (washed with 8 mL MeOH) to afford 16.3 mg of the title compound (38.9%). LC-MS m/z 700 (M+H)+, 0.66 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 and to the filtrate
  4. additionwas added MeOH (2.0 mL) and 1 drop of concentrated HCl
  5. temperatureThe solution was heated at 60° C. for 12 h
  6. customPurification
  7. dissolutionThe product was dissolved in 3 mL MeOH
  8. washwent through a 0.5 g amine column (washed with 8 mL MeOH)

Sources & evidence

ORD record
ord-4f8e619f1f9844ea82ed7a5d1111e904
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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