Pyrazole → HCID 16128672, compound

HRID 2266414Notes

Reaction equation

HRID 2266414 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C([O-])([O-])=O.[K+].[K+].[C:12]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=[CH:16][CH:15]=[C:14]([N:18]2[CH:22]=[C:21](Br)[N:20]=[CH:19]2)[CH:13]=1.CN1C(=O)CCC1>[Cl-].[Na+].O.[Cu]I.C(OCC)(=O)C.O>[C:12]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:17]=[CH:16][CH:15]=[C:14]([N:18]2[CH:22]=[C:21]([N:1]3[CH:5]=[CH:4][CH:3]=[N:2]3)[N:20]=[CH:19]2)[CH:13]=1

Participants

9

Reactant 4

HCID 1048Pyrazole2×HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidone2×HCID 59599655HCID 59599655, compound

Product 1

HCID 16128672HCID 16128672, compoundYield 32.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
180 °C

Procedure

Pyrazole (68.3 mg, 1.0 mmol), K2CO3 (139 mg, 1.0 mmol), CuI (9.5 mg, 5 mol %) and 11 (150 mg, 0.5 mmol) were added to vial and added NMP (1 mL). The slurry was heated in micro wave (emrys optimiser; fixed hold time) to 180° C. for 1 h after which after it was added NMP (1 mL) and heated to 195° C. for 3 h. The reaction mixture was then added another 6.5 mg CuI and 40 mg pyrazole, and heated for another 4 h after by which LC-MS analysis showed full conversion. The rx was added dropwise to H2O (10 mL) followed by ethyl acetate (30 mL) and brine (10 mL). The phases were separated and the aqueous phase extracted with THF (2×5 mL). The combined organic phases was washed with H2O (2×5 mL), dried (MgSO4), decanted and evaporated onto Celite and purified by CombiFlash sq16 to yield 47 mg (32%) the title compound as a white solid. HRMS (ESI+): m/z=286.3366 [M+H]

Workup

  1. temperatureheated to 195° C. for 3 h
  2. temperatureheated for another 4 h after by which LC-MS analysis
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with THF (2×5 mL)
  5. washThe combined organic phases was washed with H2O (2×5 mL)
  6. dry with materialdried (MgSO4)
  7. customdecanted
  8. customevaporated onto Celite
  9. custompurified by CombiFlash sq16

Sources & evidence

ORD record
ord-db1660c1673947babf0a6167b5c1b77e
Source dataset
uspto-grants-2010_12
Patent number
US07858649B2

Reaction notes

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