Acetic Acid → HCID 90011447, compound

HRID 1481491Notes

Reaction equation

HRID 1481491 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][N:13]=2)[N:7]=1)=O)C.BrC1C=C[C:23]([NH:26][NH2:27])=NC=1.C(O)(=[O:30])C.O=C(CC(=O)C)C(OCC)=O>C(O)C>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([N:8]2[C:9]([CH3:11])=[CH:10][C:6]([C:4]3[O:3][C:1](=[O:30])[N:26]([CH3:23])[N:27]=3)=[N:7]2)=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69208Ethyl 2,4-dioxovalerateHCID 115356995-Bromo-2-hydrazinopyridineHCID 90011572HCID 90011572, compound

Product 1

HCID 90011447HCID 90011447, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

Step-1: Ethyl-1-(5-bromopyridin-2-yl)-5-methyl-1H-pyrazole-3-carboxylate: To a stirred solution of 5-bromo-2-hydrazinylpyridine (16.6 g, 89.0 mmol), in ethanol (5 mL) and acetic acid (10 mL) was added ethyl 2,4-dioxopentanoate (14.0 g, 89.0 mmol) drop-wise at 0° C. and the resulting mixture was stirred at 100° C. for 2 h. The reaction mixture was then cooled to room temperature and the solvent was evaporated under vacuum. The residue was diluted with water (50 mL) followed by ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (100 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent) to afford 2.60 g (10%) of the title compound as white solid. 1HNMR (400 MHz, CDCl3) δ 8.51-8.50 (m, 1H), 7.96-7.93 (m, 2H), 6.71 (s, 1H), 4.41 (q, J=7.0 Hz, 2H), 2.67 (s, 3H), 1.41 (t, J=7.0 Hz, 3H); ESI-MS (m/z) 310, 312 [(MH)+, Br79,81].

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customthe solvent was evaporated under vacuum
  3. additionThe residue was diluted with water (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic layers were washed with brine (100 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customThe filtrate was rotary evaporated
  10. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent)

Sources & evidence

ORD record
ord-f9c4bd2df2ae49c39fbc748508c1bc9a
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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