1,1-dimethylethyl (2S)-4-{[3'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-5'-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate → N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(5-(methyloxy)-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamide

HRID 564605Notes

Reaction equation

HRID 564605 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:53][CH2:52][N:51](C(OC(C)(C)C)=O)[C@@H:50]([CH3:61])[CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:26]=[CH:27][CH:28]=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]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:53][CH2:52][NH:51][C@@H:50]([CH3:61])[CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[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

4

Reactant 1

HCID 670057901,1-dimethylethyl (2S)-4-{[3'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-5'-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

Product 1

HCID 57813294N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(5-(methyloxy)-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamideYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

237(b) A mixture of 1,1-dimethylethyl (2S)-4-{[3′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}-carbonyl)amino]-methyl}-5′-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (130 mg, 0.19 mmol) in 25% TFA in DCM (3 mL) was stirred at RT for 2 h. It was purified by preparative hplc (NH2OH condition), eluting with 10 to 90% CH3CN in water. The fractions were dried under GeneVac to give a solid. It was purified further using a Gilson HPLC (with 0.1% TFA condition) and eluting with 10 to 90% CH3CN in water. Fractions containing compound were combined and then converted to its free base with saturated NaHCO3. The organic layer was dried over sodium sulfate, filtered and then concentrated to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(5-(methyloxy)-3′-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamide as a white solid (58 mg, 50%). LC-MS m/z 759 (M+H)+.

Workup

  1. customIt was purified by preparative hplc (NH2OH condition)
  2. washeluting with 10 to 90% CH3CN in water
  3. customThe fractions were dried under GeneVac
  4. customto give a solid
  5. customIt was purified further
  6. washeluting with 10 to 90% CH3CN in water
  7. additionFractions containing compound
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-092d34c53e28435995ac288a4071d143
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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