N-methyl-2-pyrrolidone → tert-Butyl 3-(4-(5-(5-chloro-6-isobutylpyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate

HRID 1820992

反応式

HRID 1820992 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][C:15]=3[CH3:29])[N:10]=2)[CH:5]=[N:6][C:7]=1Cl.CN1CCCC1=O.[Br-].[CH2:38]([Zn+])[CH:39]([CH3:41])[CH3:40]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][C:15]=3[CH3:29])[N:10]=2)[CH:5]=[N:6][C:7]=1[CH2:38][CH:39]([CH3:41])[CH3:40]

参加物

6

反応物 3

HCID 13387N-methyl-2-pyrrolidoneHCID 86623617Tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoateHCID 178448254HCID 178448254、化合物

生成物 1

HCID 68891768tert-Butyl 3-(4-(5-(5-chloro-6-isobutylpyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate収率 60.3%

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 86 mg (0.20 mmol) of tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate (from EXAMPLE 15, Step A), 5.1 mg (0.01 mmol) of bis(tri-tert-butylphosphine)palladium(0), and 200 μL of 1-methyl-2-pyrrolidinone in 5.0 mL of THF was added 475 μL (0.24 mmol) of isobutylzinc bromide (0.5 M in THF). The reaction mixture was refluxed for 4 h, cooled to rt, and filtered through a cake of Celite. The filtrate was concentrated. Chromatography on Biotage 40S cartridge using 7:93 v/v Et2O/hexanes as the eluant afforded 55 mg of the title compound: 1H NMR (500 MHz, CD3OD) δ 0.99 (d, J=6.7, 6H), 1.44 (s, 9H), 2.28 (m, 1H), 2.58 (t, J=7.7, 2H), 2.66 (s, 3H), 2.93-2.97 (m, 4H), 7.18-7.20 (m, 2H), 8.01 (d, J=8.5, 1H), 8.42 (d, J=1.8, 1H), 9.22 (d, J=1.9, 1H).

後処理

  1. temperatureThe reaction mixture was refluxed for 4 h
  2. filtrationfiltered through a cake of Celite
  3. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-336a63ccd28a44c29fdab59dd792864d
出典データセット
uspto-grants-2009_10
特許番号
US07605171B2

関連ノート

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