Hydrochloric Acid → 8-[5-({[5-Methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]carbonyl}amino)pyridin-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxylic acid ethyl ester

HRID 1748621Notes

Reaction equation

HRID 1748621 reaction equation
S(Cl)(Cl)=O.[CH3:5][C:6]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:9]=[CH:8][C:7]=1[C:18]([OH:20])=O.[CH2:21]([O:23][C:24]([C:26]1([C:36]2[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][N:37]=2)[CH2:35][CH2:34][C:29]2([O:33][CH2:32][CH2:31][O:30]2)[CH2:28][CH2:27]1)=[O:25])[CH3:22].Cl>C1(C)C=CC=CC=1.N1C=CC=CC=1.CN(C)C=O>[CH2:21]([O:23][C:24]([C:26]1([C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:18]([C:7]3[CH:8]=[N:9][N:10]([C:11]4[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=4)[C:6]=3[CH3:5])=[O:20])=[CH:38][N:37]=2)[CH2:35][CH2:34][C:29]2([O:30][CH2:31][CH2:32][O:33]2)[CH2:28][CH2:27]1)=[O:25])[CH3:22]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 27695835-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carboxylic acidHCID 866924568-(5-Aminopyridin-2-yl)-1,4-dioxaspiro[4,5]decane-8-carboxylic acid ethyl ester

Product 1

HCID 866925638-[5-({[5-Methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]carbonyl}amino)pyridin-2-yl]-1,4-dioxaspiro[4.5]decane-8-carboxylic acid ethyl esterYield 81.6%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (185 mg) and N,N-dimethylformamide (catalytic amounts) were added at room temperature to a solution of 5-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carboxylic acid (210 mg) described in Reference Example 4 in toluene (3.0 ml) and stirred at 80° C. for an hour. The solvent and excess amounts of thionyl chloride were evaporated. The resulting reaction mixture of a pyridine solution (1.5 ml) was added to a solution of 8-(5-aminopyridin-2-yl)-1,4-dioxaspiro[4.5]decane-8-carboxylic acid ethyl ester (312 mg) in pyridine (1.8 ml) and stirred at 40° C. for an hour. After the reaction, the reaction solution was cooled to room temperature, adjusted to pH 4-5 by the addition of 1N hydrochloric acid aqueous solution and extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid aqueous solution, dried over anhydrous sodium sulfate and concentrated to give the titled compound (400 mg) as a white solid.

Workup

  1. customThe solvent and excess amounts of thionyl chloride were evaporated
  2. customThe resulting reaction mixture of a pyridine solution (1.5 ml)
  3. stirringstirred at 40° C. for an hour
  4. customAfter the reaction
  5. temperaturethe reaction solution was cooled to room temperature
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with 1N hydrochloric acid aqueous solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-cb7edc3cbfb346018906ab5926bb8973
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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