N,N'-Dimethylethylenediamine → 4-(4-chlorophenyl)-1-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-one

HRID 873821Notes

Reaction equation

HRID 873821 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][N:12]([CH:17]4[CH2:19][CH2:18]4)[C:11]=3[C:10](=[O:20])[NH:9]2)=[CH:4][CH:3]=1.I[C:22]1[CH:23]=[C:24]([CH3:30])[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.O1CCOCC1>[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:17]4[CH2:19][CH2:18]4)[C:11]=3[C:10](=[O:20])[N:9]2[C:22]2[CH:23]=[C:24]([CH3:30])[C:25](=[O:29])[N:26]([CH3:28])[CH:27]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 904273665-iodo-1,3-dimethylpyridin-2(1H)-oneHCID 1177027334-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Product 1

HCID 862925804-(4-chlorophenyl)-1-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-oneYield 69%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a 2-mL screw cap vial was introduced 4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 23.9) (100 mg, 0.348 mmol), 5-iodo-1,3-dimethylpyridin-2(1H)-one (Step 23.2) (104 mg, 0.417 mmol), tripotassium phosphate (148 mg, 0.695 mmol), copper(I) iodide (6.62 mg, 0.035 mmol), N,N′-dimethylethylenediamine (7.48 μL, 0.070 mmol) and dioxane (2 mL). The reaction mixture was stirred for 6 hr at 120° C., concentrated, diluted with water, and extracted with EtOAc. The combined organic layers were washed once with water, dried over Na2SO4 and evaporated. The crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-3%) followed by crystallization of the resulting residue in Et2O to provide the title product (85 mg, 0.208 mmol, 69% yield) as a white solid. tR: 4.22 min (HPLC 1); tR: 0.96 min (LC-MS 2); ESI-MS: 409 [M+H]+ (LC-MS 2); Rf=0.42 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92-1.15 (m, 2H) 1.18-1.33 (m, 2H) 1.86-2.01 (m, 6H) 3.39 (br. s., 3H) 3.75-3.90 (m, 1H) 6.08 (br. s., 1H) 7.30 (d, J=8.2 Hz, 2H) 7.36-7.47 (m, 3H) 7.75 (br. s., 1H).

Workup

  1. customIn a 2-mL screw cap vial
  2. concentrationconcentrated
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed once with water
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-3%)
  9. customfollowed by crystallization of the resulting residue in Et2O

Sources & evidence

ORD record
ord-f44ad386452f4c5ab399a1a50cbf39a1
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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