Cesium carbonate → 4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-5-(3-methyl-3H-[1,2,3]triazolo[4,5-b]-pyridin-5-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873959Notes

Reaction equation

HRID 873959 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[N:9]=[N:10][C:5]2=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[C:26]3[C:25]([CH3:27])=[N:24][N:23]([CH:28]4[CH2:30][CH2:29]4)[C:22]=3[C:21](=[O:31])[NH:20]2)=[CH:15][CH:14]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.O.CCOCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[C:26]3[C:25]([CH3:27])=[N:24][N:23]([CH:28]4[CH2:30][CH2:29]4)[C:22]=3[C:21](=[O:31])[N:20]2[C:2]2[N:7]=[C:6]3[N:8]([CH3:11])[N:9]=[N:10][C:5]3=[CH:4][CH:3]=2)=[CH:15][CH:14]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 846532705-Chloro-3-methyl-3H-[1,2,3]triazolo[4,5-B]pyridineHCID 1177027334-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Product 1

HCID 862931614-(4-chlorophenyl)-1-cyclopropyl-3-methyl-5-(3-methyl-3H-[1,2,3]triazolo[4,5-b]-pyridin-5-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-oneYield 68.5%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 5-chloro-3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine (Step 102.3) (132 mg, 0.782 mmol), 4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 85.6) (150 mg, 0.521 mmol) Pd2(dba)3 (47.7 mg, 0.052 mmol), Xantphos (60.3 mg, 0.104 mmol) and Cs2CO3 (340 mg, 1.043 mmol) in dioxane (3 mL) and the resulting mixture was heated up and stirred at 100° C. for 16 hr. The reaction was diluted with EtOAc and water and both phases separated. The aqueous layer was extracted with EtOAc, the combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. Palladium was removed using a Varian PL-Thiol MP SPE cartridge and the residue was purified by silica gel column chromatography (50% EtOAc/hexane) to afford, after trituration in Et2O, the title product (153 mg, 0.357 mmol, 68% yield) as white solid. tR: 1.20 min (LC-MS 2); ESI-MS: 420 [M+H]+ (LC-MS 2); Rf=0.24 (50% EtOAc/Hexane); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.99-1.16 (m, 2H) 1.21-1.35 (m, 2H) 1.95 (d, J=3.6 Hz, 3H) 3.87 (td, J=7.3, 3.6 Hz, 1H) 4.14 (d, J=3.7 Hz, 3H) 6.63 (d, J=3.6 Hz, 1H) 7.26-7.42 (m, 2H) 7.42-7.58 (m, 2H) 8.30-8.48 (m, 1H) 8.54 (dt, J=9.2, 3.2 Hz, 1H).

Workup

  1. temperaturethe resulting mixture was heated up
  2. customboth phases separated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organic layers were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPalladium was removed
  8. customthe residue was purified by silica gel column chromatography (50% EtOAc/hexane)
  9. customto afford

Sources & evidence

ORD record
ord-a0625580ca944c94ab065e33eee4b086
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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