Cyclopropylhydrazine → 4-(4-chlorophenyl)-1-cyclopropyl-5-(4-methoxybenzyl)-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873991Notes

Reaction equation

[CH:1]1([NH:4][NH2:5])[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[N:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:16](=[O:27])[C:15](O)=[C:14]2[C:29](=O)[CH2:30][O:31][CH3:32])=[CH:9][CH:8]=1>CCO.C1(C)C=CC=CC=1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[C:14]3[C:29]([CH2:30][O:31][CH3:32])=[N:5][N:4]([CH:1]4[CH2:3][CH2:2]4)[C:15]=3[C:16](=[O:27])[N:17]2[CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 115 °C

Procedure

Cyclopropylhydrazine (2.71 g) (Step 17.2) was added to a solution of 5-(4-chlorophenyl)-3-hydroxy-4-(2-methoxyacetyl)-1-(4-methoxybenzyl)-1H-pyrrol-2(5H)-one (5 g, 12.4 mmol) (Step 130.2) in a mixture of EtOH and toluene (60 mL, 1:1, v/v). The reaction mixture was stirred 16 h at 115° C., concentrated, quenched with a saturated aq. NaHCO3 solution, and extracted with EtOAc (2×100 mL). The combined organic layers were dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc 20-50%) to afford the title compound (2.62 g) as a yellow solid. tR: 1.24 min (LC-MS 2); ESI-MS: 438.1 [M+H]+ (LC-MS 2); Rf=0.50 (hexane/EtOAc 1:1).

Workup

concentrationconcentrated
customquenched with a saturated aq. NaHCO3 solution
extractionextracted with EtOAc (2×100 mL)
dry with materialThe combined organic layers were dried over Na2SO4
customthe solvent was evaporated off under reduced pressure
customThe crude material was purified by silica gel column chromatography (hexane/EtOAc 20-50%)

Sources & evidence

ORD record: ord-ae45ce645aca4beaaaa0dec11e6504bb
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975417B2

Reaction notes

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