Dimethyl Sulfoxide → HCID 22240510, compound

HRID 892322Notes

Reaction equation

HRID 892322 reaction equation
C([CH:3]1[CH2:8][N:7]([C:9]2[CH:14]=[CH:13][C:12](I)=[CH:11][CH:10]=2)[C:6](=[O:16])[C:5]2[N:17]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[N:18]=[C:19]([C:20]([NH2:22])=[O:21])[C:4]1=2)C.C(OC([N:41]1[CH2:46][CH2:45][NH:44][C:43](=[O:47])[CH2:42]1)=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].CS(C)=O>CCOC(C)=O.O.[Cu]I>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([N:17]2[C:5]3[C:6](=[O:16])[N:7]([C:9]4[CH:10]=[CH:11][C:12]([N:44]5[CH2:45][CH2:46][NH:41][CH2:42][C:43]5=[O:47])=[CH:13][CH:14]=4)[CH2:8][CH2:3][C:4]=3[C:19]([C:20]([NH2:22])=[O:21])=[N:18]2)=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 67242817HCID 67242817, compound

Product 1

HCID 22240510HCID 22240510, compoundYield 43.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

Part A. To ethyl-6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo (3,4-c)pyridine-3-carboxamide (0.52 g, 1.0 mmol), 4-benzyloxycarbonylpiperazin-2-one (0.32 g, 1.4 mmol), and K2CO3 (0.22 g, 1.6 mmol) was added DMSO (5 mL). The mixture was degassed with N2. CuI (38 mg, 0.2 mmol) was added and the reaction was heated to 130° C. for 18 h. The reaction was diluted with EtOAc and water, extracted with EtOAc, and dried (MgSO4). Purification by chromatography on silica gel using 5% MeOH/CH2Cl2 afforded 0.2 g (33%) of a foam; Mass Spec (M+H)+ 624.6. Part B. The product of Part A (0.2 g, 0.32 mmol) was hydrogenated at 40 psi in the presence of 10% palladium on carbon for 24 h. The reaction was filtered and then heated with 5% NH3 in ethylene gylcol in a sealed vial for 1.5 h at 80° C. The reaction was diluted with water and extracted with EtOAc. Purification by HPLC and freeze-drying afforded 30 mg (16%) of a white solid; High Resolution Mass Spec (M+H)+ for C24H25N6O4 461.1938.

Workup

  1. customThe mixture was degassed with N2
  2. extractionextracted with EtOAc
  3. dry with materialdried (MgSO4)
  4. customPurification by chromatography on silica gel using 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-bb31f3d96efd4177b9ccef3cc77e7735
Source dataset
uspto-grants-2006_02
Patent number
US07005435B2

Reaction notes

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