Water → HCID 11307256、化合物

HRID 2250430ノート

反応式

HRID 2250430 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C:14](=[O:25])[NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]3)[NH:11][C:8]2=[N:9][CH:10]=1)=[O:4].[H-].[Na+].Br[CH2:29][C:30]1[CH:34]=[C:33]([C:35]2[S:36][C:37]([Cl:40])=[CH:38][CH:39]=2)[O:32][N:31]=1.O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C:14](=[O:25])[NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH:22]([CH3:23])[CH3:24])[CH2:18][CH2:17]3)[N:11]([CH2:29][C:30]3[CH:34]=[C:33]([C:35]4[S:36][C:37]([Cl:40])=[CH:38][CH:39]=4)[O:32][N:31]=3)[C:8]2=[N:9][CH:10]=1)=[O:4]

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 69225804HCID 69225804、化合物

生成物 1

HCID 11307256HCID 11307256、化合物収率 33.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1.2 g 2-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester in 20 mL DMF, 91 mg sodium hydride (95%) were added at 0° C. Then the reaction mixture was warmed to RT and stirred for 30 min. After cooling again to 0° C., 967 mg 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole [prepared by adopting a procedure described by Ewing, William R.; Becker, Michael R.; Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, Stephen M.; Davis, Roderick S.; Hanney, Barbara A.; Spada, Alfred P.; Burns, Christopher J.; Jiang, John Z.; Li, Aiwen; Myers, Michael R.; Lau, Wan F.; Poli, Gregory B; PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] were added and the mixture was stirred for 2 h at RT. Then 50 mL of water were added and the precipitate was collected by filtration to yield 630 mg pure product. The filtrate was concentrated under reduced pressure and the residue purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). After lyophilization further 371 mg of product were obtained as a solid.

後処理

  1. temperatureAfter cooling again to 0° C.
  2. stirringthe mixture was stirred for 2 h at RT
  3. filtrationthe precipitate was collected by filtration

出典と根拠

ORDレコード
ord-ea1a9f0b8e304e62b62fe987ee3c21c1
出典データセット
uspto-grants-2008_01
特許番号
US07317027B2

反応ノート

読み込み中…