2-Methylpyridine → 3-(2-((S)-1-((S)-1,1-dimethylethylsulfinamido)-2-(pyridin-2-yl)ethyl)phenyl)benzo[d]isoxazole-6-carboxamide

HRID 475434Notes

Reaction equation

HRID 475434 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:7].C([Li])CCC.[C:13]([S@@:17](/[N:19]=[CH:20]/[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[C:31]2[CH:32]=[CH:33][C:34]([C:36]([NH2:38])=[O:37])=[CH:35][C:30]=2[O:29][N:28]=1)=[O:18])([CH3:16])([CH3:15])[CH3:14].[Cl-].[NH4+]>O1CCCC1>[CH3:15][C:13]([CH3:16])([S@@:17]([NH:19][C@H:20]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[C:31]2[CH:32]=[CH:33][C:34]([C:36]([NH2:38])=[O:37])=[CH:35][C:30]=2[O:29][N:28]=1)[CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)=[O:18])[CH3:14]

Participants

6

Reactant 4

HCID 79752-MethylpyridineHCID 25517Ammonium ChlorideHCID 889827103-[2-[(E)-[(S)-tert-butylsulfinyl]iminomethyl]phenyl]-1,2-benzoxazole-6-carboxamide2×HCID 178418339Butyllithium

Product 1

HCID 668481573-(2-((S)-1-((S)-1,1-dimethylethylsulfinamido)-2-(pyridin-2-yl)ethyl)phenyl)benzo[d]isoxazole-6-carboxamideYield 48.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a solution of 2-picoline (22.6 mL, 21.3 g) in tetrahydrofuran (280 mL) cooled under nitrogen to −72° C. was added a 2.5M in hexanes solution of n-butyl lithium (98 mL) dropwise over 40 min keeping the internal temperature less than −70° C. The mixture was stirred at this temp for 45 min then a solution of 3-(2-((E)-((S)-tert-butylsulfinylimino)methyl)phenyl)benzo[d]isoxazole-6-carboxamide (Compound 10) (28.2 g) in tetrahydrofuran (280 mL) was added dropwise over 45 min (the internal temperature less than −70° C.) then stirred at this temp for 30 min. Reaction mixture allowed to warm to −30° C. and saturated aqueous ammonium chloride (500 mL) added. The layers were separated and aqueous layer washed with ether (3×300 mL). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and the solvents removed. Flash chromatography on silica eluting with ethyl acetate then 1 to 5% methanol in ethyl acetate gave three fractions of product that were crystallised from the minimum of ethyl acetate to give the title product (17.2 g).

Workup

  1. customthe internal temperature less than −70° C
  2. stirringthen stirred at this temp for 30 min
  3. customReaction mixture
  4. customThe layers were separated
  5. washaqueous layer washed with ether (3×300 mL)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvents removed
  9. customFlash chromatography on silica eluting with ethyl acetate then 1 to 5% methanol in ethyl acetate gave three fractions of product that
  10. customwere crystallised from the minimum of ethyl acetate

Sources & evidence

ORD record
ord-afaae473476f42c685e72f3c54b5fa1d
Source dataset
uspto-grants-2014_01
Patent number
US08637551B2

Reaction notes

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