2-Methoxy-4-nitrophenol → 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3-(2-(pyridin-2-yl)ethylthio)pyrazin-2(1H)-one

HRID 562595

반응식

HRID 562595 반응식
COC1C=C([N+]([O-])=O)C=CC=1O.[OH:13][C:14]([CH3:34])([CH3:33])[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:28]=[CH:27][NH:26][C:25](=O)[C:24]2=[O:30])=[CH:19][C:18]=1[O:31][CH3:32].C(N(C(C)C)C(C)C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[N:77]1[CH:82]=[CH:81][CH:80]=[CH:79][C:78]=1[CH2:83][CH2:84][SH:85]>CN(C=O)C>[OH:13][C:14]([CH3:34])([CH3:33])[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:28]=[CH:27][N:26]=[C:25]([S:85][CH2:84][CH2:83][C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][N:77]=3)[C:24]2=[O:30])=[CH:19][C:18]=1[O:31][CH3:32]

참가 물질

7

반응물 5

HCID 767382-Methoxy-4-nitrophenolHCID 81531DiisopropylethylamineHCID 1509632-PyridineethanethiolHCID 2724699PyBOPHCID 668507271-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrazine-2,3(1H,4H)-dione2회

생성물 1

HCID 251692021-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3-(2-(pyridin-2-yl)ethylthio)pyrazin-2(1H)-one수율 68%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Following the procedures described in parts A-D of example 134, 2-methoxy-4-nitrophenol was converted to 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrazine-2,3(1H,4H)-dione. A solution of 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrazine-2,3(1H,4H)-dione prepared in Part ? (2.28 g, 7.44 mmol), EtN(iPr)2 (3.9 mL, 22.3 mmol), PyBOP (6.78 g, 13.0 mmol) in DMF (35 mL) was stirred at ambient temperature for 1.5 h. After addition of 2-pyridylethyl mercaptan (1.24 g, 8.93 mmol), the reaction was stirred at ambient temperature. After stirring overnight the reaction mixture was partially concentrated under reduced pressure, quenching by addition of aq. NaHCO3 and extracted with EtOAc. The EtOAc extracts were washed with brine, dried over MgSO4 and concentrated. Chromatography on silica employing a gradient elution with 2.5-10% methanol/methylene chloride, followed by chromatography on silica eluting with EtOAc, and trituration with EtOAc/Hexanes afforded the desired product 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3-(2-(pyridin-2-yl)ethylthio)pyrazin-2(1H)-one (2.15 g, 68% yield).

후처리

  1. stirringAfter stirring overnight the reaction mixture
  2. concentrationwas partially concentrated under reduced pressure
  3. customquenching by addition of aq. NaHCO3
  4. extractionextracted with EtOAc
  5. washThe EtOAc extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. washChromatography on silica employing a gradient elution with 2.5-10% methanol/methylene chloride

출처 및 근거

ORD 기록
ord-f981bbb9c5fe4a55bb429cbb30320eb6
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067420B2

연결된 노트

불러오는 중…