Acetic Acid → HCID 178467936, compound

HRID 1484543Notes

Reaction equation

HRID 1484543 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]=O)[CH:9]=2)[NH:4][N:3]=1.[C:13](/[CH:15]=[C:16](\[O-:18])/[CH3:17])#[N:14].[Na+].C(O)(=O)C.N1CCCCC1>ClCCl>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8](/[CH:11]=[C:15](/[C:16](=[O:18])[CH3:17])\[C:13]#[N:14])[CH:9]=2)[NH:4][N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 23687916sodium (1Z)-1-cyanoprop-1-en-2-olateHCID 178434286HCID 178434286, compound

Product 1

HCID 178467936HCID 178467936, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5.0 g (31.2 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A), 3.61 g (34.3 mmol) sodium (1Z)-1-cyanoprop-1-en-2-olate, 2.23 ml (39 mmol) acetic acid and 0.31 ml (3.12 mmol) piperidine in dry dichloromethane (250 ml) containing 4 Å molecular sieve was stirred under reflux for 12 h. Upon cooling, a precipitate was formed which was collected by filtration and washed with saturated aqueous sodium bicarbonate solution and water. The solid was dissolved in ethanol, and the molecular sieve was filtered off. The filtrate was concentrated under reduced pressure, and the residue was treated with ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed with water, dried, and concentrated under reduced pressure to afford the title compound (3.5 g, 50% of th.) as a pale yellow solid which was used in the next step without further purification.

Workup

  1. additioncontaining 4 Å molecular sieve
  2. temperatureunder reflux for 12 h
  3. temperatureUpon cooling
  4. customa precipitate was formed which
  5. filtrationwas collected by filtration
  6. washwashed with saturated aqueous sodium bicarbonate solution and water
  7. dissolutionThe solid was dissolved in ethanol
  8. filtrationthe molecular sieve was filtered off
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. additionthe residue was treated with ethyl acetate and saturated aqueous sodium carbonate solution
  11. washThe organic layer was washed with water
  12. customdried
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-69d4771fc8bd48b58c7fe188b209c051
Source dataset
uspto-grants-2016_08
Patent number
US09422263B2

Reaction notes

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