Sodium Acetate → HCID 178491042, compound

HRID 1067393Notes

Reaction equation

HRID 1067393 reaction equation
[NH2:1][C:2]1[C:6]([C:7]#[N:8])=[CH:5][NH:4][N:3]=1.[CH:9]1([O:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH:18]=O)[CH2:13][CH2:12][CH2:11][CH2:10]1.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH:9]1([O:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:18][NH:1][C:2]2[C:6]([C:7]#[N:8])=[CH:5][NH:4][N:3]=2)[CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 517045Sodium AcetateHCID 27358933-Cyclopentyloxy-4-methoxybenzaldehyde3×HCID 5003444Sodium cyanoborohydride2×HCID 178510443HCID 178510443, compound

Product 1

HCID 178491042HCID 178491042, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

A solution of 3-amino-4-cyanopyrazole (5.0 g, 0.16 mol), 3-cyclopentyloxy-4-methoxybenzaldehyde (10.0 g, 0.045 mol) and sodium acetate (0.2 g, 2.4 mol) in methanol (70 mL) was placed in a stirred reaction flask equipped with a pH stat controlling a syringe pump and syringe filled with 3 N acetic acid in methanol. The pH stat was set to maintain pH 7. After 24 hours, more 3-cyclopentyloxy-4-methoxybenzaidehyde (7.0 g, 0.031 mol) was added and the reaction was continued. After 48 hours, more 3-cyclopentyloxy-4-methoxybenzaldehyde (4.0 g, 9.0 mmol) and sodium cyanoborohydride (0.5 g, 7.9 mmol) was added and the reaction was continued. After 72 hours, more sodium cyanoborohydride (0.5 g, 7.9 mmol) was added and after 96 hours, the reaction was stopped log and the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (75mL) and water (50 mL). The ethyl acetate layer was washed with water (2×50 mL) and evaporated. The crude product was chromaotgraphed over 200 g of flash chromatography silica gel. Elution with 2% methanol/methylene chloride removed some impurities including 3-cyclopentyloxy-4-methoxybenzyl alcohol. Continued elution with methanol/methylene chloride mixtures of increasing methanol concentration afforded 8 g (56%) of nearly pure title compound. Pure 3-(3-cyclopentyloxy-4-methoxy-benzylamino)-4-cyanopyrazole, mp 159-160° was obtained by recrystallization from methanol.

Workup

  1. customequipped with a pH stat
  2. temperatureto maintain pH 7
  3. waitAfter 48 hours
  4. waitAfter 72 hours
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was partitioned between ethyl acetate (75mL) and water (50 mL)
  7. washThe ethyl acetate layer was washed with water (2×50 mL)
  8. customevaporated
  9. washElution with 2% methanol/methylene chloride
  10. customremoved some impurities
  11. washContinued elution
  12. concentrationwith methanol/methylene chloride mixtures of increasing methanol concentration

Sources & evidence

ORD record
ord-3188440d0e01420e8065cc293eeb0281
Source dataset
uspto-grants-2001_06
Patent number
US06248769B1

Reaction notes

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