2-Thiophenecarboxaldehyde → HCID 43540080, compound

HRID 1054030Notes

Reaction equation

HRID 1054030 reaction equation
[NH:1]1[CH:5]=[C:4]([NH2:6])[CH:3]=[N:2]1.[S:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[CH:12]=O>CO.C(O)(=O)C>[S:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[CH2:12][NH:6][C:4]1[CH:5]=[N:1][NH:2][CH:3]=1

Participants

5

Reactant 2

HCID 73642-ThiophenecarboxaldehydeHCID 780351H-pyrazol-4-amine

Product 1

HCID 43540080HCID 43540080, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. stirring mixture of 1H-pyrazol-4-amine (250 mg, 3.008 mmol) and thiophene-2-carbaldehyde (281 uL, 3.008 mmol) in methanol and acetic acid (5.0 ml, 10:1 ratio) was added 5-ethyl-2-methylpyridine borane complex (444 uL, 3.008 mmol). The ice bath was removed and the flask was attached to a bubbler to allow gas evolution and expansion. The reaction was stirred overnight at room temp. Most of the volatiles were evaporated in vacuo. With the aid of a 0° C. chilling bath, a 10 M solution of NaOH in water was carefully added. The ice bath was removed and stirring was continued for nearly 1 hour. The aqueous layer was extracted with DCM (3×), washed with brine, and dried over MgSO4 and concentrated. The obtained crude product was left under vacuum to remove the volatiles. The obtained viscous oil was diluted with DCM and evaporated under a gentle stream of nitrogen overnight. Solid crystals of the amine separated out and were washed with three aliquots of Hex:EtOAc=9:1. In this way, 391 mg (2.181 mmol; 72%) of the desired product were obtained in more than 97% purity by 1H-NMR analysis. 1H NMR (400 MHz, DMSO-d6) δ 4.21 (d, J=5.6 Hz, 1H), 4.92 (t, J=6.0 Hz, 1H), 6.94 (dd, J=5.1, 3.4 Hz, 1H), 7.10-6.99 (m, 3H), 7.36 (dd, J=5.1, 1.2 Hz, 1H), 12.05 (br s, 1H).

Workup

  1. additionwas added 5-ethyl-2-methylpyridine borane complex (444 uL, 3.008 mmol)
  2. customThe ice bath was removed
  3. stirringThe reaction was stirred overnight at room temp
  4. customMost of the volatiles were evaporated in vacuo
  5. temperatureWith the aid of a 0° C. chilling bath
  6. additiona 10 M solution of NaOH in water was carefully added
  7. customThe ice bath was removed
  8. stirringstirring
  9. extractionThe aqueous layer was extracted with DCM (3×)
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. customThe obtained crude product
  14. waitwas left under vacuum
  15. customto remove the volatiles
  16. additionThe obtained viscous oil was diluted with DCM
  17. customevaporated under a gentle stream of nitrogen overnight
  18. customSolid crystals of the amine separated out
  19. washwere washed with three aliquots of Hex

Sources & evidence

ORD record
ord-be78b8a0793c46a487da0ce3f0174324
Source dataset
uspto-grants-2016_07
Patent number
US09394287B2

Reaction notes

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