Methyl iodide → HCID 58573171, compound

HRID 932257Notes

Reaction equation

HRID 932257 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C@@H:14]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)[N:13]([C@@H:22]([CH2:30][CH3:31])[CH2:23][NH:24][S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])[C:12](=[O:32])[C@:11]([CH2:34][C:35]([OH:37])=[O:36])([CH3:33])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].I[CH3:41]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C@@H:14]([C:15]3[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=3)[N:13]([C@@H:22]([CH2:30][CH3:31])[CH2:23][N:24]([CH3:41])[S:25]([CH2:28][CH3:29])(=[O:26])=[O:27])[C:12](=[O:32])[C@:11]([CH2:34][C:35]([OH:37])=[O:36])([CH3:33])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68000370HCID 68000370, compound

Product 1

HCID 58573171HCID 58573171, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-((3R,5R,6S)-5-(3-chloro-5-fluorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(ethylsulfonamido)butan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 393, Step D, 26.6 mg, 0.046 mmol) in DMF (464 μl) at rt was added a dispersion of 60% sodium hydride in mineral oil (5.57 mg, 0.139 mmol). The grey slurry was stirred at rt for 30 min then iodomethane (5.80 μl, 0.093 mmol) was added. The mixture was stirred at rt for 1 h. The mixture was quenched with 1 M HCl and diluted with EtOAc. The aqueous layer was extracted with EtOAc 2×. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by reverse phase preparatory HPLC (column: Gemini™ Prep C18 10 um column; Phenomenex, Torrance, Calif.; eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes) to give the title compound.

Workup

  1. stirringThe mixture was stirred at rt for 1 h
  2. customThe mixture was quenched with 1 M HCl
  3. additiondiluted with EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc 2×
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by reverse phase preparatory HPLC (column: Gemini™ Prep C18 10 um column; Phenomenex, Torrance, Calif.; eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-804664660f264d6f874b0d291b4845ff
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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