Bromoacetonitrile → (S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-(cyanomethoxy)ethyl)-2-methylpropane-2-sulfinamide

HRID 455692Notes

Reaction equation

HRID 455692 reaction equation
O.[OH-].[Li+].[Br:4][C:5]1[CH:6]=[CH:7][C:8]([O:35][CH2:36][O:37][CH3:38])=[C:9]([C@:11]([NH:28][S@:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30])([C:14]2[CH:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:17]=[C:16]([F:26])[C:15]=2[Cl:27])[CH2:12][OH:13])[CH:10]=1.Br[CH2:40][C:41]#[N:42].[Cl-].[NH4+]>C1COCC1>[Br:4][C:5]1[CH:6]=[CH:7][C:8]([O:35][CH2:36][O:37][CH3:38])=[C:9]([C@:11]([NH:28][S@:29]([C:31]([CH3:32])([CH3:33])[CH3:34])=[O:30])([C:14]2[CH:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:17]=[C:16]([F:26])[C:15]=2[Cl:27])[CH2:12][O:13][CH2:40][C:41]#[N:42])[CH:10]=1

Participants

6

Reactant 4

HCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 67440021(S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 67438635(S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-(cyanomethoxy)ethyl)-2-methylpropane-2-sulfinamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide hydrate (0.402 g, 9.58 mmol) was added to a solution of (S)—N—((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide (1.9 g, 3.19 mmol) in THF (25 mL) at RT, followed by bromoacetonitrile (0.445 mL, 6.39 mmol). The reaction mixture was allowed to stir at RT for 12 h. The reaction mixture was treated with aqueous saturated ammonium chloride, and the mixture was extracted with EtOAc. The organic phase was washed with water, brine, dried over MgSO4 and then concentrated under reduced pressure. The remaining residue was purified by silica gel chromatography (50-100% EtOAc/hexanes) to afford 1.51 g of (S)—N—((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-(cyanomethoxy)ethyl)-2-methylpropane-2-sulfinamide.

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. washThe organic phase was washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe remaining residue was purified by silica gel chromatography (50-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-57e531de927f41e192bd3453b04ddd58
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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