Trimethyl Phosphate → (R)-8-cyclopentyl-7-ethyl-5-methyl-2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-7,8-dihydropteridin-6(5H)-one

HRID 44828

반응식

HRID 44828 반응식
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([OH:22])[CH:17]=4)[N:12]=[CH:11][C:10]=3[N:9]([CH3:23])[C:8](=[O:24])[C@H:7]2[CH2:25][CH3:26])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:27]1CCN2C(=NCCC2)CC1.P(OC)(OC)(OC)=O>O1CCOCC1>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][N:19]([CH3:27])[C:18](=[O:22])[CH:17]=4)[N:12]=[CH:11][C:10]=3[N:9]([CH3:23])[C:8](=[O:24])[C@H:7]2[CH2:25][CH3:26])[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

5

반응물 3

HCID 10541Trimethyl PhosphateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178455829HCID 178455829, 화합물

생성물 1

HCID 58405879(R)-8-cyclopentyl-7-ethyl-5-methyl-2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-7,8-dihydropteridin-6(5H)-one수율 50%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a solution of (R)-8-cyclopentyl-7-ethyl-2-(2-hydroxypyridin-4-yl)-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 14, 200 mg, 0.6 mmol) in 5 mL of 1,4-dioxane, DBU (26 mg, 3 mmol) and PO(OMe)3 (42 mg, 3 mmol) were added, and the mixture was heated to reflux for 18 h, then concentrated under reduced pressure, and extracted with EtOAc. The combined organic phase was dried with Na2SO4, concentrated under reduced pressure and the residue was chromatographed (PE:EA=1:1) to give the title compound as a yellow solid (100 mg, 50% yield). 1H NMR (CDCl3) δ: 7.95 (s, 1H), 7.53 (s, 1H) 7.35 (d, 1H), 7.11 (m, 1H), 4.54 (m, 1H), 4.29 (m, 1H), 3.6 (s, 3H), 3.38 (s, 3H), 2.2-1.6 (m, 10H) and 0.87 ppm (t, 3H); LCMS: 368.2 m/z (M+H)+; ret. Time: 1.53 min (Analytical Method E).

후처리

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated under reduced pressure
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic phase was dried with Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was chromatographed (PE:EA=1:1)

출처 및 근거

ORD 기록
ord-8b7d6c890e214626b6580a0d449eb295
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541418B2

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