Sodium hydride → tert-butyl{1-[2-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 255307노트

반응식

HRID 255307 반응식
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.FC1C=C2C(=CC=1)NC(=O)C=N2.[H-].[Na+].CS(O[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][CH:37]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36][CH2:35]1)(=O)=O>CN(C=O)C.O.C(OCC)C>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](=[O:12])[N:9]2[CH2:32][CH2:33][N:34]2[CH2:39][CH2:38][CH:37]([NH:40][C:41](=[O:42])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:36][CH2:35]2)=[CH:4][CH:3]=1

참가 물질

8

반응물 4

HCID 24758Sodium hydrideHCID 126863866-Fluoro-1,2-dihydroquinoxalin-2-one2회HCID 217275347-fluoroquinoxalin-2(1H)-one2회HCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2회

생성물 1

HCID 59397942tert-butyl{1-[2-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

A suspension of a 1:1 mixture of 7-fluoroquinoxalin-2(1H)-one (Intermediate 143) and 6-fluoroquinoxalin-2(1H)-one (Intermediate 144) (1.5 g total, 9.1 mmol) was treated with sodium hydride (60% in oil, 0.44 g, 11.0 mmol) at 0° C. The reaction was allowed to stir at room temperature for 2 hours. The reaction mixture was cooled to 0° C. and 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6, 1.33 mmol/mL, 11.0 mmol), dissolved in dry DMF (5 mL) was added and it was stirred at room temperature overnight. The reaction mixture was diluted with water and with diethyl ether (5×50 mL). The combined organic phases were dried over sodium sulfate and concentrated to dryness under reduced pressure. Chromatography with hexanes/acetone (5:1 to 3:1). The higher Rf material was isolated as a mixture of Intermediate 141 with an O-alkylated isomer, which was rechromatographed on silica gel with hexanes/ethyl acetate (1:3) to give pure Intermediate 141 as a colorless solid, 0.24 g, 14%. Isolation of the lower Rf material from the first column gave 0.38 g (21%) of pure Intermediate 142 as a colorless solid.

후처리

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. additionwas added
  3. stirringit was stirred at room temperature overnight
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated to dryness under reduced pressure

출처 및 근거

ORD 기록
ord-60c8af2b8e4149f6baa9842477922232
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07875715B2

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