Hydrochloric Acid → 4-Chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-methanol

HRID 1576816Notes

Reaction equation

HRID 1576816 reaction equation
C([O:3][C:4]([C:6]1[C:7]([Cl:18])=[C:8]2[C:14]([CH3:15])=[N:13][N:12]([CH2:16][CH3:17])[C:9]2=[N:10][CH:11]=1)=O)C.O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O>[Cl:18][C:7]1[C:6]([CH2:4][OH:3])=[CH:11][N:10]=[C:9]2[N:12]([CH2:16][CH3:17])[N:13]=[C:14]([CH3:15])[C:8]=12

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8028TetrahydrofuranHCID 1473447ethyl 4-chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 213152334-Chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-methanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

63 g. of 4-Chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (0.235 mol.) are dissolved in 360 ml. of anhydrous tetrahydrofuran. Nitrogen is passed through the flask and while stirring and cooling with tap water, 5.2 g. of lithium aluminium hydride is added a bit at a time so that the reaction temperature does not exceed 25°. Stirring is continued for 2 hours at room temperature. Without further stirring the reaction mixture is allowed to stand over night. Then 300 ml. of 3N-hydrochloric acid is added while stirring and cooling with ice-water to keep the temperature between 15° and 20°. The clear solution is evaporated to dryness in vacuo, the residue is treated with 100 ml of water and precipitated starting material (5-6 g.) is filtered off. Then the filtrate is diluted with 300 ml. of water and refrigerated over night. 32- 39.3 g. (60-74%) of 4-chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-methanol which crystallizes is filtered and dried at 70°, m.p. 119°-21°. The compound is recrystallized from acetonitrile, m.p. 121°-122°. Acidification of the aqueous mother liquor with hydrochloric acid, evaporation in vacuo and extraction of the residue by means of boiling acetonitrile yielded up to 15 g. of the starting material in form of the hydrochloride.

Workup

  1. customdoes not exceed 25°
  2. stirringStirring
  3. stirringWithout further stirring the reaction mixture
  4. waitto stand over night
  5. stirringwhile stirring
  6. customthe temperature between 15° and 20°
  7. customThe clear solution is evaporated to dryness in vacuo
  8. additionthe residue is treated with 100 ml of water
  9. customprecipitated
  10. filtrationis filtered off
  11. additionThen the filtrate is diluted with 300 ml
  12. waitof water and refrigerated over night
  13. custom(60-74%) of 4-chloro-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-methanol which crystallizes
  14. filtrationis filtered
  15. customdried at 70°
  16. customThe compound is recrystallized from acetonitrile, m.p. 121°-122°
  17. customAcidification of the aqueous mother liquor with hydrochloric acid, evaporation
  18. extractionin vacuo and extraction of the residue by means of boiling acetonitrile
  19. customyielded up to 15 g

Sources & evidence

ORD record
ord-c20ca9a716ca40b5b56c9bd6f86d5890
Source dataset
uspto-grants-1976_09
Patent number
US03983128

Reaction notes

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