Cesium carbonate → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(6-(2-hydroxypropan-2-yl)pyridazin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1046070

反応式

HRID 1046070 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:42]=[N:41][C:40]([C:43]([OH:46])([CH3:45])[CH3:44])=[CH:39][CH:38]=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]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:37]3[N:42]=[N:41][C:40]([C:43]([OH:46])([CH3:45])[CH3:44])=[CH:39][CH:38]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 595261612-(6-Chloropyridazin-3-yl)propan-2-olHCID 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 58485360(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(6-(2-hydroxypropan-2-yl)pyridazin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

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 solution 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 (50 mg, 0.104 mmol), 2-(6-chloropyridazin-3-yl)-propan-2-ol (20 mg, 0.151 mmol), Pd(PPh3)2Cl2 (30 mg, 0.046 mmol), 2 M aq Cs2CO3 (0.4 mL) in dioxane (5 mL) was heated at reflux for 2 h. The reaction mixture was concentrated, and the residue was treated with water (20 mL) and extracted with EtOAc (3×10 mL). The combined organic layer was washed with satd aq NaCl solution, dried with anhydrous Na2SO4, and concentrated to give an oil, which was purified by preparative TLC and HPLC to give the product. LC-MS Method 2 tR=1.031 min, m/z=490.3; 1H NMR (CD3OD): δ0.89 (s, 1H), 0.96 (s, 3H), 1.28 (m, 6H), 1.57 (d, 3H), 1.66 (m, 6H), 2.15 (s, 2H), 2.28 (m, 1H), 2.56 (m, 2H), 3.08 (m, 1H), 5.62 (m, 1H), 7.13 (d, 2H), 7.38 (m, 5H), 7.82 (m, 2H), 8.05 (m, 2H).

後処理

  1. temperatureat reflux for 2 h
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was treated with water (20 mL)
  4. extractionextracted with EtOAc (3×10 mL)
  5. washThe combined organic layer was washed with satd aq NaCl solution
  6. dry with materialdried with anhydrous Na2SO4
  7. concentrationconcentrated
  8. customto give an oil, which
  9. customwas purified by preparative TLC and HPLC
  10. customto give the product

出典と根拠

ORDレコード
ord-40f53c513d5844cab00ecb3768a51852
出典データセット
uspto-grants-2013_10
特許番号
US08569292B2

関連ノート

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