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

Reaction equation

HRID 44828 reaction equation
[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

Participants

5

Reactant 3

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

Product 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)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-8b7d6c890e214626b6580a0d449eb295
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Linked notes

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