HCID 57813320, compound → 3-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}oxy)methyl]-N-{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}benzamide

HRID 564597Notes

Reaction equation

HRID 564597 reaction equation
Cl[CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40][OH:41])[CH:35]=2)=[O:33])=[CH:26][C:25]=1[C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]2[CH2:54][CH2:53][N:52](C(OC(C)(C)C)=O)[CH2:51][CH2:50]2)[CH:43]=1>CN(C=O)C>[CH2:14]([N:11]1[C:6]2=[N:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:2][O:41][CH2:40][C:36]3[CH:35]=[C:34]([CH:39]=[CH:38][CH:37]=3)[C:32]([NH:31][CH2:30][C:27]3[CH:26]=[C:25]([C:42]4[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]5[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]5)[CH:43]=4)[C:24]([F:23])=[CH:29][CH:28]=3)=[O:33])[C:4]([NH:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:5]2[CH:13]=[N:12]1)[CH3:15]

Participants

4

Reactant 2

HCID 57813320HCID 57813320, compoundHCID 596832285-(chloromethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine2×

Product 1

HCID 441808773-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}oxy)methyl]-N-{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}benzamideYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(chloromethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (73.9 mg, 0.229 mmol) in DMF (0.5 mL) was added 1,1-dimethylethyl 4-({2′-fluoro-5′-[({[3-(hydroxymethyl)phenyl]carbonyl}-amino)methyl]-3-biphenylyl}methyl)-1-piperazinecarboxylate (122 mg, 0.229 mmol). The mixture was stirred at room temperature for 15 h then more 5-(chloro-methyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-amine (73.9 mg, 0.229 mmol) was added. The mixture was stirred for another 24 h. The reaction was quenched with H2O (1 drop), diluted with MeOH (0.5 mL), purified using a Gilson HPLC (with TFA). To the Fractions containing the product was added TFA (1 drop in each tube ˜12 mL) and solvent was concentrated on a GeneVav EZ-2 evaporator. The compound was purified again with a Gilson HPLC (with TFA) and concentrated on GeneVav EZ-2 evaporator. Residue was basified with an amine cartridge to afford 0.0095 g (6%) of the title compound. LC-MS m/z 720 (M+H)+; 1H-NMR (400 MHz, CD3OD) δ ppm 1.29 (t, J=7.65 Hz, 3 H) 1.50 (t, J=7.28 Hz, 3 H) 1.62-1.75 (m, 2 H) 1.97-2.06 (m, 2 H) 2.96 (q, J=7.53 Hz, 2 H) 3.38-3.47 (m, 4 H) 3.47-3.54 (m, J=4.52 Hz, 4 H) 3.56-3.64 (m, 2 H) 3.85-3.93 (m, 2 H) 4.25-4.33 (m, 1 H) 4.36 (s, 2 H) 4.47 (q, J=7.28 Hz, 2 H) 4.60 (s, 2 H) 4.70 (s, 2 H) 4.83 (s, 2 H) 7.19 (dd, J=10.67, 8.41 Hz, 1H) 7.37-7.43 (m, 1 H) 7.46-7.59 (m, 5 H) 7.65 (d, J=6.78 Hz, 1 H) 7.72 (s, 1 H) 7.81 (d, J=7.78 Hz, 1 H) 7.89 (s, 1 H) 8.27 (s, 1 H).

Workup

  1. stirringThe mixture was stirred for another 24 h
  2. customThe reaction was quenched with H2O (1 drop)
  3. additiondiluted with MeOH (0.5 mL)
  4. custompurified
  5. additionTo the Fractions containing the product
  6. additionwas added TFA (1 drop in each tube ˜12 mL) and solvent
  7. concentrationwas concentrated on a GeneVav EZ-2 evaporator
  8. customThe compound was purified again with a Gilson HPLC (with TFA)
  9. concentrationconcentrated on GeneVav EZ-2 evaporator

Sources & evidence

ORD record
ord-298415d133cc4d70a0f0a9c0d3d448b4
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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