Hydrochloric Acid → 1-(3-chloro-4-fluorophenyl)-6-[4-iodophenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 1611806Notes

Reaction equation

HRID 1611806 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][NH2:10])[CH:5]=[CH:6][C:7]=1[F:8].[I:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([C:24](=O)[C:25]([F:28])([F:27])[F:26])[C:20](=O)[C:19]2=[O:31])=[CH:14][CH:13]=1.C(O)C.Cl>C(OC(=O)C)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:20]3[C:19](=[O:31])[N:18]([C:15]4[CH:16]=[CH:17][C:12]([I:11])=[CH:13][CH:14]=4)[CH2:23][CH2:22][C:21]=3[C:24]([C:25]([F:28])([F:26])[F:27])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 27365753-Chloro-4-fluorophenylhydrazineHCID 222404772,3-Piperidinedione, 1-(4-iodophenyl)-4-(2,2,2-trifluoroacetyl)-

Product 1

HCID 222404461-(3-chloro-4-fluorophenyl)-6-[4-iodophenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-oneYield 75%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Part A. 3-chloro-4-fluorophenyl hydrazine (5.00 g, 31.14 mmol) and 1-(4-iodophenyl)-4-(trifluoroacetyl)-2,3-piperidinedione (12.8 g, 31.14 mmol) were added together with 120 mL of ethanol and 4 mL of hydrochloric acid (12 M). The mixture was stirred at reflux under N2 for overnight. The reaction was cooled down to rt. The solvents were removed, and the residue was dissolved in EtOAc (200 mL) and washed with water (100 mL×2) and brine (50 mL). It was then dried over Na2SO4 and concentrated. The residue was purified via flash chromatography on silica gel using 4:1 hexane:ethylacetate to give 1-(3-chloro-4-fluorophenyl)-6-[4-iodophenyl]-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridine-7-one as a brown solid (12.5 g, 75% yield). LRMS (AP+): 536.1 (M+H)+. 1H NMR (CDCl3) δ 7.72 (d, 2H), 7.67-7.64 (m, 1H), 7.49-7.44 (m, 1H), 7.19 (t, 3H), 7.06 (d, 2H), 4.12 (t, 2H), 3.17 (t, 2H).

Workup

  1. temperatureat reflux under N2 for overnight
  2. customThe solvents were removed
  3. dissolutionthe residue was dissolved in EtOAc (200 mL)
  4. washwashed with water (100 mL×2) and brine (50 mL)
  5. dry with materialIt was then dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified via flash chromatography on silica gel using 4:1 hexane

Sources & evidence

ORD record
ord-03720d08c7c84157866e8165bfbc1106
Source dataset
uspto-grants-2006_01
Patent number
US06989391B2

Reaction notes

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