Cesium carbonate → methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate

HRID 1512770ノート

反応式

HRID 1512770 の反応式
Br[C:2]1[C:10]2[C:5](=[C:6]([C:11]3[N:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[C:18]([Cl:26])[CH:17]=4)[O:13][N:12]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]([CH3:27])[CH:3]=1.CC(P(C(C)(C)C)C(C)(C)C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Br[Zn][CH2:49][C@@H:50]([CH3:55])[C:51]([O:53][CH3:54])=[O:52]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:26][C:18]1[CH:17]=[C:16]([C:14]2[O:13][N:12]=[C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[N:4]([CH3:27])[CH:3]=[C:2]4[CH2:49][C@@H:50]([CH3:55])[C:51]([O:53][CH3:54])=[O:52])[N:15]=2)[CH:21]=[CH:20][C:19]=1[O:22][CH:23]([CH3:24])[CH3:25]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 591461473-bromo-7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indoleHCID 178501471HCID 178501471、化合物

生成物 1

HCID 59146133methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of 3-bromo-7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole (D59) (100 mg), tris(1,1-dimethylethyl)phosphane (13 mg), Pd2(dba)3 (41 mg) and Cs2CO3 (30 mg) in THF (5 mL) stirred under nitrogen at room temperature was added a solution of bromo[(2S)-2-methyl-3-(methyloxy)-3-oxopropyl]zinc (1.0 M in THF, 2 mL) in one portion. The reaction mixture was stirred at 60° C. for 1.5 h. The mixture was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with water, aqueous HCl (2 M) and brine, dried over sodium sulphate and evaporated to afford methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate (D60) (120 mg). MS (ES): C25H26ClN3O4 requires 467; found 468.2 (M+H+).

後処理

  1. stirringThe reaction mixture was stirred at 60° C. for 1.5 h
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. washThe organic phase was washed with water, aqueous HCl (2 M) and brine
  6. dry with materialdried over sodium sulphate
  7. customevaporated

出典と根拠

ORDレコード
ord-5bb20d42774a48578a70b73b3ed48684
出典データセット
uspto-grants-2012_07
特許番号
US08217028B2

反応ノート

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