HCID 118511053, compound → HCID 118511175, compound

HRID 1478200Notes

Reaction equation

HRID 1478200 reaction equation
[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([C@H:22]4[CH2:27][CH:26]=[C:25]([CH3:28])[CH2:24][O:23]4)[O:18][N:17]=3)=[O:15])=[C:9]([CH3:29])[N:8]2[CH3:30])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(N2C(=O)C(NC(C3C(C)=C([C@@H]4CC=C(C)CO4)ON=3)=O)=C(C)N2C)CCCCC1>CCO.[Pd]>[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([C@H:22]4[CH2:27][CH2:26][C@@H:25]([CH3:28])[CH2:24][O:23]4)[O:18][N:17]=3)=[O:15])=[C:9]([CH3:29])[N:8]2[CH3:30])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 118511053HCID 118511053, compoundHCID 118511160HCID 118511160, compound

Product 1

HCID 118511175HCID 118511175, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a mixture of (R)—N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-5-(5-methyl-3,6-dihydro-2H-pyran-2-yl)isoxazole-3-carboxamide compound and (S)—N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-5-(5-methyl-3,6-dihydro-2H-pyran-2-yl)isoxazole-3-carboxamide (1:1) (Example 21.2) (35 mg, 0.084 mmol) in EtOH (15 mL) under a flow of nitrogen was added Pd—C (3.59 mg, 0.034 mmol). The reaction mixture was stirred at room temperature under an atmosphere of hydrogen at 0.35 bar for 2 hours. The resulting mixture was filtered through Celite®, washing with Ethanol. The filtrate was concentrated under reduced pressure and passed through a 1 g Biotage Silica-TMT cartridge under gravity. The cartridge was washed with ethanol and the eluent was concentrated under reduced pressure. The crude material was dissolved in DMSO and purified using UV-directed automated reverse phase chromatography over a 9.5 minute gradient of 30-70% MeCN in water (0.1% formic acid). The product fractions were added to EtOAc (30 mL) and washed with saturated aqueous NaHCO3 (30 mL). The organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound;

Workup

  1. filtrationThe resulting mixture was filtered through Celite®
  2. washwashing with Ethanol
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. washThe cartridge was washed with ethanol
  5. concentrationthe eluent was concentrated under reduced pressure
  6. dissolutionThe crude material was dissolved in DMSO
  7. custompurified
  8. customover a 9.5 minute
  9. additionThe product fractions were added to EtOAc (30 mL)
  10. washwashed with saturated aqueous NaHCO3 (30 mL)
  11. dry with materialThe organic extracts were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5ca238b044d4409aad9383ed174f05ab
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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