Dimethylamine → (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester

HRID 19154ノート

反応式

HRID 19154 の反応式
CC1(C)O[C@H](CN2C=CC(N[C:14](=[O:35])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28](Br)[C:27]=4[F:33])=[CH:22][C:21]3=[O:34])[CH2:16][CH:17]([CH3:19])[CH3:18])=N2)CO1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:89][NH:90][CH3:91].[O:92]1CC[CH2:94][CH2:93]1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH2:93]([O:92][C:14](=[O:35])[C@@H:15]([N:20]1[CH2:24][C:23]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N:90]([CH3:91])[CH3:89])[C:27]=2[F:33])=[CH:22][C:21]1=[O:34])[CH2:16][CH:17]([CH3:18])[CH3:19])[CH3:94]

参加物

9

反応物 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 44252757(S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1 H-pyrazol-3-yl]-amide

生成物 1

HCID 66894887(S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester収率 34%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a mixture of (S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (prepared as in Example 128, 0.850 g, 2.05 mmol), palladium(II) acetate (0.050 g, 0.22 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.250 g, 0.40 mmol), and cesium carbonate (1.90 g, 5.83 mmol) in 1,4-dioxane (5 mL) was added a dimethylamine solution in tetrahydrofuran (2M, 3 mL, 6.00 mmol) and the resulting mixture was sealed in a tube and heated at 100° C. for 6 h. The cooled solution was poured into ethyl acetate (100 mL), filtered and the filtrate washed with water, brine and dried over anhydrous sodium sulfate. The resulting mixture was filtered, evaporated and the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g, 10% to 60% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (0.261 g, 34%) as a yellow oil.

後処理

  1. customthe resulting mixture was sealed in a tube
  2. filtrationfiltered
  3. washthe filtrate washed with water, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe resulting mixture was filtered
  6. customevaporated
  7. customthe residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g, 10% to 60% ethyl acetate/hexanes) which

出典と根拠

ORDレコード
ord-f846ea16b1d64146a3a55f1198b9b177
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

読み込み中…