4-Bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine → 5-Bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole

HRID 1157720

反応式

HRID 1157720 の反応式
O(C(C)(C)C)[K].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:15]#[C:16][CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH:20]2[CH3:24])[CH:9]=1>CN1C(=O)CCC1>[Br:7][C:8]1[CH:9]=[C:10]2[C:11](=[CH:12][CH:13]=1)[NH:14][C:16]([CH2:17][CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH3:24])=[CH:15]2

参加物

4

反応物 2

HCID 219800934-Bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamineHCID 178418922HCID 178418922、化合物

生成物 1

HCID 210414975-Bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole収率 61.2%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒2 回

実験手順

To a cooled (0° C.) suspension of KO-tBu (95%, 7.8 g, 66 mmol) in NMP (150 mL) was added a solution of 4-bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine (10 g, 33 mmol) in NMP (50 mL) dropwise keeping the temperature below 5° C. The resulting mixture was then stirred at room temperature for 3 hours under nitrogen. HPLC indicated that all the starting material was consumed. H2O (400 mL) was added slowly to the reaction mixture followed by addition of IPAc (500 mL). The resulting mixture was stirred for 5 min. and the organic layer was separated. The organic layer was then washed with 20% brine (3×200 mL), dried over Na2SO4 and treated with activated carbon. After filtration, the filtrate was concentrated under reduced pressure to give the title compound as a thick oil (6.2 g), which was used in the next coupling reaction without further purification. 1H NMR (400 MHz, CDCl3) δ 10.21 (s, 1H), 7.73 (s, 1H), 7.27 (s, 2H), 6.24 (s, 1H), 3.42-3.50 (m, 1H), 3.21-3.28 (m, 1H), 2.97-3.10 (m, 2H), 2.49-2.60 (m, 2H), 2.33 (q, J=8.78 Hz, 1H), 2.10-2.17 (m, 1H), 1.87-2.02 (m, 2H), 1.58-1.67 (m, 1H), 1.24 (d, J=6.2 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ 140.89, 133.92, 129.91, 122.98, 121.77, 112.16, 111.75, 98.32, 60.47, 53.60, 53.34, 33.19, 26.30, 22.14, 19.56. [M+H]+ at m/z 307.

後処理

  1. temperatureTo a cooled
  2. customthe temperature below 5° C
  3. customwas consumed
  4. additionH2O (400 mL) was added slowly to the reaction mixture
  5. additionfollowed by addition of IPAc (500 mL)
  6. stirringThe resulting mixture was stirred for 5 min.
  7. customthe organic layer was separated
  8. washThe organic layer was then washed with 20% brine (3×200 mL)
  9. dry with materialdried over Na2SO4
  10. additiontreated with activated carbon
  11. filtrationAfter filtration
  12. concentrationthe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-e6bae259fe4e4cd3a323c7e64842a693
出典データセット
uspto-grants-2010_10
特許番号
US07807697B2

関連ノート

読み込み中…