2,2'-Bipyridine → 4-(4-chlorophenyl)-1-cyclopropyl-5-(4-methoxybenzyl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873944Notes

Reaction equation

HRID 873944 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][NH:12][C:11]=3[C:10](=[O:17])[N:9]2[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:4][CH:3]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.C([O-])([O-])=O.[Na+].[Na+].N1C=CC=CC=1C1C=CC=CN=1>ClCCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][N:12]([CH:27]4[CH2:29][CH2:28]4)[C:11]=3[C:10](=[O:17])[N:9]2[CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 14742,2'-BipyridineHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 178490844HCID 178490844, compound

Product 1

HCID 1177026894-(4-chlorophenyl)-1-cyclopropyl-5-(4-methoxybenzyl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-oneYield 32%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-(4-chlorophenyl)-5-(4-methoxybenzyl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 85.4) (8.76 g, 23.82 mmol) in 1,2-dichloroethane (100 mL) were added cyclopropylboronic acid (4.09 g, 47.6 mmol), copper (II) acetate (5.19 g, 28.6 mmol), Na2CO3 (5.05 g, 47.6 mmol) and 2,2′-bipyridine (3.72 g, 23.82 mmol) and the resulting mixture was stirred 16 h at 70° C. The reaction mixture was quenched with a saturated aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with saturated aq. NaHCO3 solution, dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc 15-30%) to afford the title product (3.27 g, 7.62 mmol, 32% yield) as yellow solid. tR: 5.77 min (HPLC 1); tR: 1.27 min (LC-MS 2); ESI-MS: 408 [M+H]+ (LC-MS 2); Rf=0.65 (hexane/EtOAc 1:1).

Workup

  1. customThe reaction mixture was quenched with a saturated aq. NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with saturated aq. NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc 15-30%)

Sources & evidence

ORD record
ord-db4eb0e51689447facc622d94d23e1c4
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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