5-hydrazinyl-1-methyl-1H-pyrazole → 4-(4-chlorophenyl)-5-(4-methoxybenzyl)-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-one

HRID 873978Notes

Reaction equation

HRID 873978 reaction equation
[C:1]([C:4]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[N:7]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:6](=[O:25])[C:5]=1O)(=O)[CH3:2].[NH:27]([C:29]1[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=1)[NH2:28]>CCO.C1(C)C=CC=CC=1>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([CH:8]2[C:4]3[C:1]([CH3:2])=[N:28][N:27]([C:29]4[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=4)[C:5]=3[C:6](=[O:25])[N:7]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 684257025-hydrazinyl-1-methyl-1H-pyrazoleHCID 1177028964-acetyl-5-(4-chlorophenyl)-3-hydroxy-1-[(4-methoxyphenyl)methyl]-2,5-dihydro-1H-pyrrol-2-one

Product 1

HCID 1177027824-(4-chlorophenyl)-5-(4-methoxybenzyl)-3-methyl-1-(1-methyl-1H-pyrazol-5-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-oneYield 85.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a stirred solution of 4-acetyl-5-(4-chlorophenyl)-3-hydroxy-1-(4-methoxybenzyl)-1H-pyrrol-2(5H)-one (Step 71.2) (3 g, 8.07 mmol) in EtOH (50 mL) and toluene (50 mL) was added 5-hydrazinyl-1-methyl-1H-pyrazole (Step 74.2) (1.941 g, 10.49 mmol) and the resulting mixture was heated up and stirred at 115° C. for 20 hr. The reaction was quenched with a saturated aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane/EtOAc 40-50%) to afford the title product (3.15 g, 6.89 mmol, 85% yield) as yellow solid. tR: 5.60 min (HPLC 1); tR: 1.24 min (LC-MS 2); ESI-MS: 448 [M+H]+ (LC-MS 2); Rf=0.41 (hexane/EtOAc 1:1).

Workup

  1. temperaturethe resulting mixture was heated up
  2. customThe reaction was quenched with a saturated aq. NaHCO3 solution
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel column chromatography (hexane/EtOAc 40-50%)

Sources & evidence

ORD record
ord-5880acb5d1534a64bed68a7a41bded1f
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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