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 455692ノート

反応式

HRID 455692 の反応式
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

参加物

6

反応物 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

生成物 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-sulfinamide収率 74.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-57e531de927f41e192bd3453b04ddd58
出典データセット
uspto-grants-2013_07
特許番号
US08497264B2

反応ノート

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