Cesium carbonate → BI-135585

HRID 406695ノート

反応式

HRID 406695 の反応式
I[C:2]1[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=1.[OH:10][C:11]([CH3:44])([CH3:43])[CH2:12][C@@:13]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:18][C:17](=[O:19])[N:16]([C@H:20]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[CH3:21])[CH2:15][CH2:14]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:10][C:11]([CH3:43])([CH3:44])[CH2:12][C@@:13]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:18][C:17](=[O:19])[N:16]([C@H:20]([C:22]2[CH:23]=[CH:24][C:25]([C:2]3[CH:7]=[CH:6][N:5]([CH3:8])[C:4](=[O:9])[CH:3]=3)=[CH:26][CH:27]=2)[CH3:21])[CH2:15][CH2:14]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

生成物 1

HCID 44476893BI-135585収率 28%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 4-iodo-1-methylpyridin-2(1H)-one (0.909 g, 3.76 mmol), (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (1.5 g, 3.13 mmol), 2 M aq Cs2CO3 (3 mL, 6 mmol), and PdCl2(PPh3)2 (0.201 g, 0.282 mmol) in 1,4-dioxane (15 mL) was refluxed under N2 for 2 hours. The reaction mixture was filtered, and the filtrate was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to obtain the crude compound, which was purified by preparative HPLC and chiral HPLC to obtain (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (399 mg, 28%). LC-MS and 1H NMR (CD3OD) were the same as those of product made by Method 1. The compound was recrystallized using below methods.

後処理

  1. temperaturewas refluxed under N2 for 2 hours
  2. filtrationThe reaction mixture was filtered
  3. extractionthe filtrate was extracted with EtOAc
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto obtain the crude compound, which
  8. customwas purified by preparative HPLC and chiral HPLC

出典と根拠

ORDレコード
ord-bb56e96ca5e243b899fc37bf050289ee
出典データセット
uspto-grants-2014_06
特許番号
US08754076B2

反応ノート

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