Sodium Carbonate → 4-Chloro-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

HRID 1284639Notes

Reaction equation

HRID 1284639 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:18])=[C:8]2[CH:15]=[N:14][N:13](CC)[C:9]2=[N:10][C:11]=1[CH3:12])=[O:5])[CH3:2].NC1N(CC)N=CC=1.BrN1C(=O)CCC1=O.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)(Cl)Cl.C1COCC1.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:18])=[C:8]2[CH:15]=[N:14][NH:13][C:9]2=[N:10][C:11]=1[CH3:12])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 67184N-bromobutanimideHCID 3373101-Ethyl-1H-pyrazol-5-amineHCID 13059311Ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

Product 1

HCID 135604464-Chloro-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl esterYield 54.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 10.0 g (37.4 mM) of 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, prepared according to Examples 1b. and 1c. from 5-amino-1-ethyl-pyrazole in place of 5-amino-1-pentylpyrazole, and 7.65 g (43.0 mM) of N-bromosuccinimide in 75 ml of carbon tetrachloride was illuminated with a sunlamp and stirred under N2 at gentle reflux for 2 hours. The cooled reaction mixture was filtered and the filtrate concentrated to leave an orange residue which was dissolved in 50 ml of THF. 35 ml of saturated aqueous sodium carbonate were added, and the mixture was stirred vigorously at room temperature for 18 hours and then diluted with water and extracted with ethyl acetate. The combined extracts were dried with MgSO4, filtered and concentrated to leave a white solid which was chromatographed over silica gel using the solvent system of ethyl acetate:hexane (1:3) as the eluant. The fractions containing the desired product were combined and concentrated to leave a white solid. Recrystallization of the solid from toluene/hexane gave 4.88 g of the desired ester as white needles, mp=156°-157.5° C.; tlc, Rf =0.2, silica gel, ethyl acetate:hexane (1:3).

Workup

  1. customprepared
  2. temperatureat gentle reflux for 2 hours
  3. customThe cooled reaction mixture
  4. filtrationwas filtered
  5. concentrationthe filtrate concentrated
  6. customto leave an orange residue which
  7. stirringthe mixture was stirred vigorously at room temperature for 18 hours
  8. extractionextracted with ethyl acetate
  9. dry with materialThe combined extracts were dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto leave a white solid which
  13. customwas chromatographed over silica gel using the solvent system of ethyl acetate:hexane (1:3) as the eluant
  14. additionThe fractions containing the desired product
  15. concentrationconcentrated
  16. customto leave a white solid
  17. customRecrystallization of the solid from toluene/hexane

Sources & evidence

ORD record
ord-75eb95f11b294b21b0d39d3238a4b52f
Source dataset
uspto-grants-1986_01
Patent number
US04563525

Reaction notes

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