Potassium Carbonate → 2-(2-Pyrrolidin-1-yl-ethyl)-2,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 586717Notes

Reaction equation

HRID 586717 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][N:15]=[CH:16][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl[CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2=[N:14][N:15]([CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:16]=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 103986805-Boc-1,4,6,7-tetrahydropyrazolo[4,3-C]pyridine

Product 1

HCID 208259562-(2-Pyrrolidin-1-yl-ethyl)-2,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

1,4,6,7-Tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.8 g, 8.06 mmol)(EP1057814, Example 2c) was added to 1-(2-chloro-ethyl)-pyrrolidine hydrochloride (1.65 g, 9.67 mmol) and potassium carbonate (3.34 g, 24.2 mmol) in N,N-dimethylformamide (35 ml) and the mixture was heated at 65° C. for 26 hours, then cooled to room temperature and stirred for 72 hours. The solvent was evaporated under reduced pressure and the residue was dissolved in 2N sodium hydroxide solution. The aqueous mixture was extracted with ethyl acetate (×2) and the combined organic layers were dried over magnesium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using ammonium hydroxide, methanol and ethyl acetate in dichloromethane as eluant (gradient from 0:0:50:50 to 0:0.1:50:50 to 0.5:5:0:95) to give the title compounds from preparation 228-A and preparation 228-B as a mixture of isomers (300 mg). LRMS: m/z ES+ 321 [MH+]

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in 2N sodium hydroxide solution
  4. extractionThe aqueous mixture was extracted with ethyl acetate (×2)
  5. dry with materialthe combined organic layers were dried over magnesium sulphate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-a88a80660ee348d9b807ce7759e5dfb0
Source dataset
uspto-grants-2005_08
Patent number
US06936619B2

Reaction notes

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