Potassium Hydroxide → Arry-382

HRID 79406

반응식

HRID 79406 반응식
Cl[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH:31]3[CH2:33][CH2:32]3)=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[OH-].[K+].[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][OH:45])[CH2:39][CH2:38]1>O.CS(C)=O.C1COCC1>[CH:31]1([C:16]2[C:15]3[C:19](=[CH:20][CH:21]=[CH:22][C:14]=3[NH:13][C:11]([C:8]3[N:5]4[CH:6]=[CH:7][C:2]([O:45][CH2:44][CH2:43][N:40]5[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]5)=[CH:3][C:4]4=[N:10][CH:9]=3)=[O:12])[N:18]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)[N:17]=2)[CH2:32][CH2:33]1

참가 물질

7

반응물 3

HCID 14797Potassium HydroxideHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 672599697-chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

생성물 1

HCID 67259771Arry-382수율 73.8%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매2회HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
95 °C

실험 절차

7-Chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (5.0 g, 10.9 mmol), potassium hydroxide (3.38 g, 60.2 mmol), DMSO (50 mL), and 2-(4-methylpiperazin-1-yl)ethanol (3.16 g, 21.9 mmol) were combined under nitrogen and heated to 95° C. for 16 hours. The mixture was cooled to ambient temperature and THF (300 mL) was added. The slurry was stirred at ambient temperature for 3 hours. The solids were filtered off and the THF removed from the filtrates under vacuum to give a DMSO solution of the product. The DMSO solution was heated to 60° C. and water (100 mL) was added to precipitate out the product. The slurry was cooled to ambient temperature and stirred for 18 hours. The solids were collected by filtration and washed with water (100 mL) and MTBE (50 mL). The material was dried under vacuum at 40° C. to give N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide (4.54 g). MS (ES+APCI) m/z=565.1 (M+H).

후처리

  1. temperatureThe mixture was cooled to ambient temperature
  2. filtrationThe solids were filtered off
  3. customthe THF removed from the filtrates under vacuum
  4. customto give a DMSO solution of the product
  5. customto precipitate out the product
  6. temperatureThe slurry was cooled to ambient temperature
  7. stirringstirred for 18 hours
  8. filtrationThe solids were collected by filtration
  9. washwashed with water (100 mL) and MTBE (50 mL)
  10. customThe material was dried under vacuum at 40° C.

출처 및 근거

ORD 기록
ord-7a1ab28010b64060abcb2787594553ba
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841455B2

연결된 노트

불러오는 중…