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

HRID 2037763ノート

反応式

HRID 2037763 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.Br[C:37]1[CH:38]=[CH:39][CH2:40][N:41]([CH:43]([CH3:45])[CH3:44])[CH:42]=1.C([O-])([O-])=[O:47].[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: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[CH:38]=[CH:39][C:40](=[O:47])[N:41]([CH:43]([CH3:45])[CH3:44])[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 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-oneHCID 866499515-Bromo-1-isopropylpyridin

生成物 1

HCID 59635784(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-isopropyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one収率 21%

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

To 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 (100 mg, 0.21 mmol) in 1,4-dioxane (2 mL) was added 5-bromo-1-isopropylpyridin-2(1H-one (54.2 mg, 0.25 mmol). Then catalysts of Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), Cs2CO3 (1 mL, 2 M) were added. The vessel was sealed with a septum and placed into the microwave cavity. Microwave irradiation of 100 W was used, the temperature being ramped from room temperature to 120° C. Once this temperature was reached, the reaction mixture was held at this temperature for 30 min. After the mixture cooled to rt, the mixture was filtered. The filtrate was extracted with EtOAc (20 mL×4), the organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product which was purified by preparative HPLC to give (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(1-isopropyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (22 mg, 21%). 1H NMR (CDCl3): 1.13 (s, 3H), 1.19 (s, 3H), 1.40 (6H), 1.53 (d, 3H), 2.18-2.30 (m, 4H), 2.40 (m, 1H), 2.88 (m, 1H), 5.31 (m, 1H), 5.70 (m, 1H), 6.73 (d, 1H), 7.02 (d, 2H), 7.15 (d, 2H), 7.27-7.38 (m, 5H), 7.43 (d, 1H), 7.50 (d, 1H).

後処理

  1. customThe vessel was sealed with a septum
  2. customMicrowave irradiation of 100 W
  3. custombeing ramped from room temperature to 120° C
  4. filtrationthe mixture was filtered
  5. extractionThe filtrate was extracted with EtOAc (20 mL×4)
  6. washthe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto give the crude product which
  10. customwas purified by preparative HPLC

出典と根拠

ORDレコード
ord-4f8338c6eef54747b67b984b53d9385a
出典データセット
uspto-grants-2013_11
特許番号
US08575156B2

反応ノート

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