Pyrazole → HCID 118117834, compound

HRID 1747212Notes

Reaction equation

HRID 1747212 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[CH2:5][C@H:6]1[NH:11][C:10](=[O:12])[CH2:9][O:8][CH2:7]1.[NH:16]1[CH:20]=[CH:19][CH:18]=[N:17]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C.[Cu]Cl>[N:16]1([C:2]2[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=2)[CH2:5][C@H:6]2[NH:11][C:10](=[O:12])[CH2:9][O:8][CH2:7]2)[CH:20]=[CH:19][CH:18]=[N:17]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 118117552HCID 118117552, compound

Product 1

HCID 118117834HCID 118117834, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-5-(3-iodo-benzyl)-morpholin-3-one A-10 (1.0 g, 3.15 mmol), pyrazole (322 mg, 4.73 mmol), K2CO3 (872 mg, 6.31 mmol), copper(I) chloride (31 mg, 0.32 mmol) and L-proline (73 mg, 0.63 mmol) in DMF (8 mL) was heated under argon to 110° C. for 24 h. The reaction mixture was cooled to RT and partitioned between water and DCM before being filtered through a celite plug. The layers were separated and the aqueous phase was re-extracted with DCM (2×). The combined organic phases were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo to give the crude product that was purified by flash chromatography (eluting with a gradient of 50% to 100% EtOAc in hexane) to give the title compound as a white solid. LC-MS B: tR=0.51 min; [M+H]+=257.86.

Workup

  1. custompartitioned between water and DCM
  2. filtrationbefore being filtered through a celite plug
  3. customThe layers were separated
  4. extractionthe aqueous phase was re-extracted with DCM (2×)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give the crude product that
  10. customwas purified by flash chromatography (
  11. washeluting with a gradient of 50% to 100% EtOAc in hexane)

Sources & evidence

ORD record
ord-f9d3d2cc4db44732bc248d6139ccf792
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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