Dichloromethane → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({3'-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)butanediamide

HRID 657424Notes

Reaction equation

HRID 657424 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:28][CH3:29])=[C:10]([CH2:19][NH:20][C:21](=[O:27])[CH2:22][CH2:23][C:24]([OH:26])=O)[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].[CH3:30][N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][C:38]2[CH:39]=[C:40]([C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([CH2:50][NH2:51])[CH:45]=3)[CH:41]=[CH:42][CH:43]=2)[CH2:33][CH2:32]1.C(N(CC)CC)C.ClCCl>CCOC(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:28][CH3:29])=[C:10]([CH2:19][NH:20][C:21](=[O:27])[CH2:22][CH2:23][C:24]([NH:51][CH2:50][C:46]3[CH:45]=[C:44]([C:40]4[CH:41]=[CH:42][CH:43]=[C:38]([CH2:37][CH:34]5[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]5)[CH:39]=4)[CH:49]=[CH:48][CH:47]=3)=[O:26])[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 6344DichloromethaneHCID 8471TriethylamineHCID 57813254({3'-[(1-Methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)amineHCID 578198724-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-4-oxobutanoic acid

Product 1

HCID 44242690N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({3'-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)butanediamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-4-oxobutanoic acid (0.080 g, 0.198 mmol), (({3′-[(1-methyl-4-piperidinyl)methyl]-3-biphenylyl}methyl)amine, triethylamine (0.080 mL, 0.575 mmol) and dichloromethane (DCM) (3 mL) was stirred at room temperature overnight. The LC-MS suggested that the reaction was complete. The reaction was diluted with EtOAc and washed in turn with sat. aq. NaHCO3, then saturated aqueous NaCl. The organic phase was dried (Na2SO4) and evaporated to give a residue (175 mg). This residue was purified on a Gilson HPLC on RP column CH3CN—H2O (0.1% TFA) gradient [10-80%]. Fractions containing the desired product were combined and evaporated to a small volume, then treated with saturated aqueous NaHCO3. The mixture was extracted with EtOAc (2×) and the combined extracts were washed with saturated aqueous NaCl and dried (Na2SO4), then evaporated to a glassy solid (52.2 mg). LC-MS m/z 680.7 (M+H)+, 0.76 min (ret time).

Workup

  1. washwashed in turn with sat. aq. NaHCO3
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated

Sources & evidence

ORD record
ord-524bd5028c344c708221c9dc5fbc81da
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…