p-Toluenesulfonic acid monohydrate → HCID 178513505, compound

HRID 270967Notes

Reaction equation

HRID 270967 reaction equation
C[O:2][C:3](=O)[CH:4]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[C:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)=O.[NH2:28][C:29]1[NH:33][N:32]=[C:31]([C:34]([NH2:36])=[O:35])[CH:30]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:14]([O:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[NH:28][C:29]3[N:33]([N:32]=[C:31]([C:34]([NH2:36])=[O:35])[CH:30]=3)[C:3](=[O:2])[C:4]=2[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:12][CH:11]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 588250313-(4-Benzyloxy-phenyl)-2-cyclohexyl-3-oxo-propionic acid methyl esterHCID 178513689HCID 178513689, compound

Product 1

HCID 178513505HCID 178513505, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1.0 g (2.7 mmol) of 3-(4-benzyloxy-phenyl)-2-cyclohexyl-3-oxo-propionic acid methyl ester, 340 mg (2.7 mmol) of 5-amino-1H-pyrazole-3-carboxylic acid amide, 51 mg (10 mol %) of p-toluenesulfonic acid monohydrate (PTSA), and 15 mL of toluene was heated at reflux for 72 h. The reaction mixture was then concentrated to a residue which chromatographed on silica gel (Biotage; gradient elution 15% ethyl acetate in dichloromethane to 6% methanol in dichloromethane) to give a residue which was further purified via reverse-phase chromatography (Gilson) to afford (after lyophilization) 22 mg (2% yield) of desired 5-(4-benzyloxy-phenyl)-6-cyclohexyl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid amide as indicated by 1H-NMR; LC-MS calcd for C26H26N4O3 [M++H]+: 443.2, found: 443.2.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 72 h
  3. concentrationThe reaction mixture was then concentrated to a residue which
  4. customchromatographed on silica gel (Biotage; gradient elution 15% ethyl acetate in dichloromethane to 6% methanol in dichloromethane)
  5. customto give a residue which
  6. customwas further purified via reverse-phase chromatography (Gilson)

Sources & evidence

ORD record
ord-086528215ed746baa54d5303e4a67a3c
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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