Pyrazole → HCID 118117606, compound

HRID 1747216Notes

Reaction equation

HRID 1747216 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[O:16][CH3:17])[CH2:5][C@H:6]1[NH:11][C:10](=[O:12])[CH2:9][O:8][CH2:7]1.[NH:18]1[CH:22]=[CH:21][CH:20]=[N:19]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C.[Cu]Cl>[CH3:17][O:16][C:15]1[CH:14]=[CH:13][C:4]([CH2:5][C@H:6]2[NH:11][C:10](=[O:12])[CH2:9][O:8][CH2:7]2)=[CH:3][C:2]=1[N:18]1[CH:22]=[CH:21][CH:20]=[N:19]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 118117188HCID 118117188, compound

Product 1

HCID 118117606HCID 118117606, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-5-(3-iodo-4-methoxy-benzyl)-morpholin-3-one C-7 (60 mg, 0.17 mmol), pyrazole (18 mg, 0.30 mmol), K2CO3 (48 mg, 0.35 mmol), copper(I) chloride (1.7 mg, 0.02 mmol) and L-proline (4 mg, 0.04 mmol) in DMF (1 mL) was heated under argon to 110° C. for 168 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 (Biotage SP1, 10 g SNAP-cartridge eluting with 95:5 DCM:MeOH) to give the title compound as a brown oil. LC-MS B: tR=0.53 min; [M+H]+=288.16.

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 (Biotage SP1, 10 g SNAP-cartridge eluting with 95:5 DCM:MeOH)

Sources & evidence

ORD record
ord-9240e3dcf9b446b6b777f31dd3315678
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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