Morpholine → 4-({1,6-Diethyl-5-[({[4-(4-{[4-(4-morpholinyl)butyl]oxy}butyl)phenyl]carbonyl}amino)methyl]-1H-pyrazolo[3,4-b]pyridin-4-yl}amino)-1-piperidinecarboxamide

HRID 1675696Notes

Reaction equation

HRID 1675696 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([NH:19][CH2:20][C:21]2[C:22]([NH:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([NH2:43])=[O:42])[CH2:37][CH2:36]3)=[C:23]3[CH:31]=[N:30][N:29]([CH2:32][CH3:33])[C:24]3=[N:25][C:26]=2[CH2:27][CH3:28])=[O:18])=[CH:13][CH:12]=1.C(N(CC)C(C)C)(C)C.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>CN(C)C=O>[CH2:32]([N:29]1[C:24]2=[N:25][C:26]([CH2:27][CH3:28])=[C:21]([CH2:20][NH:19][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH2:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:53]4[CH2:58][CH2:57][O:56][CH2:55][CH2:54]4)=[CH:12][CH:13]=3)=[O:18])[C:22]([NH:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([NH2:43])=[O:42])[CH2:37][CH2:36]3)=[C:23]2[CH:31]=[N:30]1)[CH3:33]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 580247424-{[5-({[(4-{4-[(4-Bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide2×

Product 1

HCID 249851264-({1,6-Diethyl-5-[({[4-(4-{[4-(4-morpholinyl)butyl]oxy}butyl)phenyl]carbonyl}amino)methyl]-1H-pyrazolo[3,4-b]pyridin-4-yl}amino)-1-piperidinecarboxamideYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-{[5-({[(4-{4-[(4-bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide (1.1 g, 1.67 mmol, e.g. which can be as prepared in Intermediate 28) in N,N-dimethylformamide (20 ml) was treated with N,N-diisopropylethylamine (0.567 ml) and morpholine (0.300 ml, 3.3 mmol) and heated at 65° C. The solvent was removed under vacuum and the residue was applied directly to a 100 g silica SPE cartridge and eluted with a gradient of from 0% to 50% methanol in dichloromethane over 40 mins. Fractions containing product were pooled and evaporated to give a pale orange foam which appeared to be about 85% pure by analytical HPLC. The residue was further purified by mass directed preparative HPLC (Method C, using 0.1% trifluoroacetic acid) in 50 mg portions, and, following evaporation of the solvent from the appropriate fractions, the residual material was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate solution (NaHCO3). The organic fraction was collected by passing through a hydrophobic frit and evaporated to give the title compound (0.300 g) as a white foam. LCMS showed MH+=663; TRET=2.09 min.

Workup

  1. customThe solvent was removed under vacuum
  2. washeluted with a gradient of from 0% to 50% methanol in dichloromethane over 40 mins
  3. additionFractions containing product
  4. customevaporated
  5. customto give a pale orange foam which
  6. customThe residue was further purified by mass
  7. customevaporation of the solvent from the appropriate fractions
  8. dissolutionthe residual material was dissolved in dichloromethane
  9. washwashed with saturated aqueous sodium bicarbonate solution (NaHCO3)
  10. customThe organic fraction was collected
  11. customevaporated

Sources & evidence

ORD record
ord-ac311de78456453ba10afea1dd64d5b1
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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