Water → HCID 11307256, 화합물

HRID 2250430노트

반응식

HRID 2250430 반응식
[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]

참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 69225804HCID 69225804, 화합물

생성물 1

HCID 11307256HCID 11307256, 화합물수율 33.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-ea1a9f0b8e304e62b62fe987ee3c21c1
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07317027B2

반응 노트

불러오는 중…