Dimethylformamide → HCID 86692583, compound

HRID 1748642Notes

Reaction equation

HRID 1748642 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[CH3:7][N:8]([CH3:11])C=O.[C:12]([C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:26]([CH3:27])=[C:25]([C:28]([OH:30])=O)[CH:24]=[N:23]2)=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]>ClCCl>[C:12]([C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:26]([CH3:27])=[C:25]([C:28]([NH:22][C:26]3[CH:7]=[N:8][C:11]([CH:16]4[CH2:21][CH2:20][C:19]5([O:5][CH2:1][CH2:2][O:3]5)[CH2:18][CH2:17]4)=[CH:24][CH:25]=3)=[O:30])[CH:24]=[N:23]2)=[CH:18][CH:17]=1)([CH3:14])([CH3:15])[CH3:13]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 82089556HCID 82089556, compound

Product 1

HCID 86692583HCID 86692583, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.25 ml) and N,N-dimethylformamide (catalytic amounts) were added at room temperature to a solution of 1-(4-tert-butylphenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (222 mg) described in Reference Example 17 in dichloromethane (5 ml) and stirred at room temperature for two hours. The solvent and an excess amount of oxalyl chloride were evaporated. Toluene (5 ml) was added to the resulting reaction mixture, a solution of 6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridine-3-amine (185 mg) described in Reference Example 102 in pyridine (4 ml) was added under ice-cooling, and stirred at room temperature overnight. After the reaction, 1N aqueous solution of sodium hydroxide was added under ice-cooling and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated. The resulting residue was purified with a silica gel column chromatography (n-hexane/ethyl acetate) and ethanol was added to give 1-(4-tert-butylphenyl)-N-[6-(1,4-dioxaspiro[4.5]decan-8-yl)pyridin-3-yl]-5-methyl-1H-pyrazole-4-carboxamide (242 mg) as a white solid.

Workup

  1. customThe solvent and an excess amount of oxalyl chloride were evaporated
  2. additionToluene (5 ml) was added to the resulting reaction mixture
  3. additionwas added under ice-
  4. temperaturecooling
  5. stirringstirred at room temperature overnight
  6. customAfter the reaction, 1N aqueous solution of sodium hydroxide
  7. additionwas added under ice-
  8. temperaturecooling
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customThe resulting residue was purified with a silica gel column chromatography (n-hexane/ethyl acetate) and ethanol
  13. additionwas added

Sources & evidence

ORD record
ord-d7974afd324a4fc58ed9bc40898ddd75
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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