Acetohydrazide → N'-acetyl-2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetohydrazide

HRID 2074104Notes

Reaction equation

HRID 2074104 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13](O)=[O:14])[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[C:36]([NH:39][NH2:40])(=[O:38])[CH3:37]>C1COCC1.CN(C=O)C.O>[C:36]([NH:39][NH:40][C:13](=[O:14])[CH2:12][N:11]1[C:7]([CH2:6][C:5]2[CH:22]=[CH:23][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:8][C:9]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[N:10]1)(=[O:38])[CH3:37]

Participants

7

Reactant 3

HCID 14039AcetohydrazideHCID 682631,1'-CarbonyldiimidazoleHCID 670925255-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acid

Product 1

HCID 67092526N'-acetyl-2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetohydrazide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (300 mg, 0.96 mmol) in THF (5 mL) and DMF (2 mL) was added CDI (345 mg, 2.12 mmol) and the suspension sonicated for 5 minutes to give a solution that was stirred for 2 hours at room temperature. To this was added acetic hydrazide (210 mg, 2.89 mmol) and the resulting suspension stirred for 18 hours at room temperature. The resulting suspension was diluted with water (50 mL) and the solid filtered off and washed with water (30 mL) and EtOAc (50 mL) to yield pure N′-acetyl-2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetohydrazide. This was suspended in THF (5 mL) then Burgess' reagent (279 mg, 1.17 mmol) was added and the mixture heated to reflux for 2 hours. The reaction was cooled to ambient temperature, the volatiles removed in vacuo, and the residue was taken into EtOAc (50 mL) and washed with water (2×50 mL), brine (50 mL), dried over MgSO4, filtered and stripped. The residue was purified by Biotage flash chromatography, eluting with 1-4% MeOH/DCM to afford the title compound as a white solid, 200 mg, 73%. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 8.50-8.68 (2 H, m), 7.52-7.70 (2 H, m), 7.16 (2 H, dd, J=8.59, 5.31 Hz), 6.93-7.08 (2 H, m), 6.44 (1 H, s), 5.40 (2 H, s), 4.08 (2 H, s), 2.47 (3 H, s); m/z (APCI+) for C19H16N5FO 350.1 (M+H)+.

Workup

  1. customthe suspension sonicated for 5 minutes
  2. customto give a solution that
  3. stirringthe resulting suspension stirred for 18 hours at room temperature
  4. filtrationthe solid filtered off
  5. washwashed with water (30 mL) and EtOAc (50 mL)

Sources & evidence

ORD record
ord-a4e98515a0214ff18329535091aac9c9
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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