Acetic Acid → HCID 178437836, compound

HRID 1597867Notes

Reaction equation

HRID 1597867 reaction equation
[Na].[CH:2]1([N:7]2[C:11]([NH2:12])=[C:10]([C:13]([NH2:15])=[O:14])[C:9]([CH2:16][CH3:17])=[N:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[N:18]1([CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:38]=[CH:37][CH:36]=[CH:35][C:29]=2[C:30](OCC)=O)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(O)(=O)C>C(O)C.O.CCOCC>[CH:2]1([N:7]2[C:11]3=[N:12][C:30]([C:29]4[CH:35]=[CH:36][CH:37]=[CH:38][C:28]=4[O:27][CH2:26][CH2:25][CH2:24][N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)=[N:15][C:13](=[O:14])[C:10]3=[C:9]([CH2:16][CH3:17])[NH:8]2)[CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 410450HCID 410450, compoundHCID 5360545SodiumHCID 224493525-amino-1-cyclopentyl-3-ethyl-1H-pyrazole-4-carboxamide

Product 1

HCID 178437836HCID 178437836, compoundYield 65.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

Sodium spheres (0.42 g) were dissolved in ethanol (20 ml) and then 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (2.02 g, 9.10 mmol) was added, followed by ethyl 2-[3-(4-morpholinyl)propoxy]benzoate (5.33 g). The reaction mixture was refluxed for 3 days, then stirred at room temperature, and then the solvent was stripped. The residue was dissolved in water (250 ml), acidified to a pH of about 7 with acetic acid and extracted with CHCl3. The organic layers were washed with brine, dried over MgSO4 and stripped to afford an oil. The oil was taken up in ether, filtered and the filtrate was stripped and purified by column chromatography on silica eluting with EtOAc (100%) followed by EtOAc/MeOH (80/20) to afford 2.71 g of 1-cyclopentyl-3-ethyl-6-[2-[3-(4-morpholinyl)propoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-one, as a liquid [labelled as Example 26(b)]. The free base was treated with EtOH.HCl and 1.14 g of the hydrochloride salt (labelled as Example 26(c) was obtained, m.p. 220°-221° C.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 days
  2. extractionextracted with CHCl3
  3. washThe organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customto afford an oil
  6. filtrationfiltered
  7. custompurified by column chromatography on silica eluting with EtOAc (100%)

Sources & evidence

ORD record
ord-9f10cbee9a904da789ded2fe188b5d31
Source dataset
uspto-grants-1998_04
Patent number
US05736548

Reaction notes

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