Acetic Acid → 1,1-dimethylethyl 4-[(5'-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-1-piperazinecarboxylate

HRID 662091Notes

Reaction equation

HRID 662091 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[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:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=O)[CH:41]=5)[C:36]([CH3:39])=[CH:37][CH:38]=4)=[O:30])[N:24]=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].[N:50]1([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>ClCCCl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[N:24]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:38]=[CH:37][C:36]([CH3:39])=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][N:53]6[CH2:54][CH2:55][N:50]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:51][CH2:52]6)[CH:41]=5)[CH:34]=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]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2724942TriacetoxyborohydrideHCID 57819380N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

Product 1

HCID 578193851,1-dimethylethyl 4-[(5'-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-1-piperazinecarboxylateYield 76.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (1.85 g, 2.80 mmol) and 1,1-dimethylethyl 1-piperazinecarboxylate (1.055 g, 5.61 mmol) were dissolved in 1,2-dichloroethane (30 mL) and acetic acid (0.177 ml, 3.08 mmol) was added. The mixture was stirred for 30 minutes and then MP-Triacetoxyborohydride (3.61 g, 8.41 mmol) was added. The mixture was stirred overnight. It was then filtered through a glass fiber filter paper and washed 2× with 20 mL of DCE. The solvent was evaporated and the residue was taken up in methylene chloride and absorbed on Isolute® Sorbent and purified on a Combiflash on an 80 g silica column eluted with 0-10% MeOH/CH2Cl2. Product fractions were combined and concentrated under vacuum to give 1,1-dimethylethyl 4-[(5′-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2′-methyl-3-biphenylyl)methyl]-1-piperazinecarboxylate (1.8 g, 2.140 mmol, 76% yield) as a white solid. LC-MS m/z 830 (M+H)+, 0.86 min (ret time).

Workup

  1. stirringThe mixture was stirred overnight
  2. filtrationIt was then filtered through a glass fiber
  3. filtrationfilter paper
  4. washwashed 2× with 20 mL of DCE
  5. customThe solvent was evaporated
  6. customabsorbed on Isolute® Sorbent
  7. custompurified on a Combiflash on an 80 g silica column
  8. washeluted with 0-10% MeOH/CH2Cl2
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b8570238169c4fd98a42104691dc8d9c
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

Loading…