Acetic Acid → HCID 9951707, compound

HRID 1278887Notes

Reaction equation

HRID 1278887 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=2F)[N:5]=[CH:4][C:3]=1[C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]=O)[CH:17]=1.[NH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.Cl.C(OCC)(=O)C>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH:17]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 22262776HCID 22262776, compound

Product 1

HCID 9951707HCID 9951707, compoundYield 60.6%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-amino-1-(2,4-difluorophenyl)-4-[3-formylbenzoyl]pyrazole (0.3 g, 0.92 mmol), piperidine (0.1 ml, 1.0 mmol), acetic acid (0.05 ml) in 1,2-dichloroethane (5 ml) was added sodium triacetoxyborohydride (0.29 g, 1.37 mmol). After stirring at room temperature for 12 hours, the reaction was diluted with 10% hydrochloric acid and ethyl acetate (10 ml). The aqueous layer was separated and neutralized to pH 9 with sodium hydroxide and was then extracted with ethyl acetate. The combined organics were separated and washed with brine (25 ml), dried over MgSO4 and then concentrated in vacuo to a brown oil. The oil was purified by flash column chromatography using 1:1 hexanes/ethyl acetate to remove impurities and ethyl acetate to elute the desired product. Concentration of the column fractions in vacuo gave 5-amino-1-(4-fluorophenyl)-4-[3-(1-piperidinylmethyl)-benzoyl]pyrazole as an oil (0.211 g). The compound was triturated to a solid from hexanes/ethyl acetate.

Workup

  1. customThe aqueous layer was separated
  2. extractionwas then extracted with ethyl acetate
  3. customThe combined organics were separated
  4. washwashed with brine (25 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo to a brown oil
  7. customThe oil was purified by flash column chromatography
  8. customto remove impurities and ethyl acetate
  9. washto elute the desired product

Sources & evidence

ORD record
ord-85a6e06532e343e194646fbf2ab22586
Source dataset
uspto-grants-2002_09
Patent number
US06444696B1

Reaction notes

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