Acetic Acid → 1-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4-(3-(trifluoromethoxy)phenyl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-one

HRID 873949Notes

Reaction equation

HRID 873949 reaction equation
[C:1]([CH:4]1[CH:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:19])([F:18])[F:17])[CH:10]=2)[N:7]([C:20]2[CH:25]=[C:24]([CH3:26])[C:23](=[O:27])[N:22]([CH3:28])[CH:21]=2)[C:6](=[O:29])[C:5]1=O)(=O)[CH3:2].Cl.[CH:32]1([NH:35][NH2:36])[CH2:34][CH2:33]1.CC(O)=O>O1CCOCC1>[CH:32]1([N:35]2[C:5]3[C:6](=[O:29])[N:7]([C:20]4[CH:25]=[C:24]([CH3:26])[C:23](=[O:27])[N:22]([CH3:28])[CH:21]=4)[CH:8]([C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:19])([F:18])[F:17])[CH:10]=4)[C:4]=3[C:1]([CH3:2])=[N:36]2)[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 19594967Hydrazine, cyclopropyl-, hydrochloride (1:1)HCID 1177028004-Acetyl-1-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-5-(3-(trifluoromethoxy)-phenyl)pyrrolidine-2,3-dione

Product 1

HCID 862933491-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4-(3-(trifluoromethoxy)phenyl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-oneYield 18.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 4-acetyl-1-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-5-(3-(trifluoromethoxy)-phenyl)pyrrolidine-2,3-dione (Step 91.1) (50 mg, 0.118 mmol) in Dioxane (1 mL) were added cyclopropylhydrazine hydrochloride (Step 17.2) (25.7 mg, 0.237 mmol) and TEA (0.082 mL, 0.592 mmol) and the resulting mixture was heated up and stirred at 120° C. for 2 hr. AcOH was added to acidify the reaction mixture and stirred at 100° C. for 30 min. The reaction was cooled down to RT and concentrated under reduced pressure. The residue was dissolved in EtOAc and washed with a saturated aq. NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (CH2Cl2/(CH2Cl2/MeOH 19:1 NH3) 0-100%) to afford the title product (10 mg, 0.021 mmol, 18.1% yield) as yellow foam. tR: 1.03 min (LC-MS 2); ESI-MS: 459 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04 (d, J=6.3 Hz, 2H) 1.24 (br. s., 3H) 1.93 (s, 6H) 3.37-3.39 (m, 1H) 3.81 (br. s., 1H) 6.13 (s, 1H) 7.22-7.57 (m, 5H) 7.76 (br. s., 1H).

Workup

  1. temperaturethe resulting mixture was heated up
  2. stirringstirred at 100° C. for 30 min
  3. temperatureThe reaction was cooled down to RT
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in EtOAc
  6. washwashed with a saturated aq. NaHCO3 solution and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by silica gel column chromatography (CH2Cl2/(CH2Cl2/MeOH 19:1 NH3) 0-100%)

Sources & evidence

ORD record
ord-67ae0af5a2614f35a9b79bcacc3b24d6
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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