Hydrochloric Acid → 1-(5-Chloro-6-methylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid

HRID 1748448Notes

Reaction equation

HRID 1748448 reaction equation
[ClH:1].C([O:4][C:5]([C:7]1[CH:8]=[N:9][N:10]([C:13]2[CH:18]=[CH:17][C:16](N)=[C:15]([CH3:20])[N:14]=2)[C:11]=1[CH3:12])=[O:6])C.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+]>[Cu]Cl.O>[Cl:1][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[C:11]([CH3:12])=[C:7]([C:5]([OH:4])=[O:6])[CH:8]=[N:9]2)=[N:14][C:15]=1[CH3:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 23668193Sodium Nitrite2×HCID 866924121-(5-amino-6-methylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 866924191-(5-Chloro-6-methylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent

Procedure

Water (4 ml) and concentrated hydrochloric acid (1 ml) were added to 1-(5-amino-6-methylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (260 mg) described in Reference Example 31(3), and then sodium nitrite (83 mg) was added therein at 0° C. After stirring for 0.5 hour, sodium nitrite (83 mg) was added again and stirred for an hour. Then copper (I) chloride (485 mg) was added and stirred in a water bath for 20 minutes. The reaction solution was added to a saturated aqueous solution of sodium bicarbonate and filtered through Celite. Water was added to the filtrate, extracted with ethyl acetate and the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was reacted and treated in a similar manner as Reference Example 24(3) to give the titled compound (112 mg) as a brown solid.

Workup

  1. customat 0° C
  2. stirringstirred for an hour
  3. stirringstirred in a water bath for 20 minutes
  4. filtrationfiltered through Celite
  5. additionWater was added to the filtrate
  6. extractionextracted with ethyl acetate
  7. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was reacted

Sources & evidence

ORD record
ord-d562cab9a65841a78fa2d2d677cdbda6
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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