Cesium carbonate → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

HRID 2045994ノート

反応式

HRID 2045994 の反応式
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Cl[C:37]1[N:38]=[CH:39][C:40](=[O:44])[N:41]([CH3:43])[CH:42]=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:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[N:38]=[CH:39][C:40](=[O:44])[N:41]([CH3:43])[CH:42]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 584852805-Chloro-1-methylpyrazin-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 44512093(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one収率 71.5%

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 (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 (279 mg, 0.6 mmol) and 5-chloro-1-methyl-1H-pyrazin-2-one (70 mg, 0.5 mmol), Pd(Ph3P)2Cl2 (3 mg), and aq. Cs2CO3 solution (0.5 mL, 2M) in 1,4-dioxane (3 mL) was stirred at reflux for 2.5 h under N2. When the reaction was over, the mixture was washed with water, and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated to give the crude product, which was purified by preparative TLC to give (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (165.1 mg, 34.6%). LC-MS Method 2 tR=1.107 min, m/z=404.1; 1H NMR (CDCl3): δ 1.11 (s, 3H), 1.18 (s, 3H), 1.54 (d, 3H), 2.35 (m, 4H), 2.87 (m, 1H), 3.62 (s, 3H), 5.69 (m, 1H), 7.05 (d, 2H), 7.34 (m, 5H), 7.45 (m, 1H), 7.50 (d, 2H), 8.25 (s, 1H).

後処理

  1. temperatureat reflux for 2.5 h under N2
  2. washwas washed with water
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by preparative TLC

出典と根拠

ORDレコード
ord-058d792453974e59906b8d94b8b5391b
出典データセット
uspto-grants-2013_11
特許番号
US08592410B2

反応ノート

読み込み中…