Potassium Carbonate → 7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-8-((6-methylpyridin-3-yl)oxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200710Notes

Reaction equation

HRID 2200710 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][C:22]3([OH:25])[CH2:24][CH2:23]3)[C:6](=[O:26])[N:5]([CH3:27])[C:4]=2[N:3]=1.[CH3:28][C:29]1[N:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:10]2[C:9]3[C:8](=[O:19])[N:7]([CH2:20][CH2:21][C:22]4([OH:25])[CH2:24][CH2:23]4)[C:6](=[O:26])[N:5]([CH3:27])[C:4]=3[N:3]=[C:2]2[O:35][C:32]2[CH:33]=[N:34][C:29]([CH3:28])=[CH:30][CH:31]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 142752-Methyl-5-hydroxypyridineHCID 904028418-bromo-7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione2×

Product 1

HCID 904030877-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-8-((6-methylpyridin-3-yl)oxy)-1H-purine-2,6(3H,7H)-dioneYield 80.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-bromo-7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (128 mg, 0.282 mmol, intermediate 56) in DMF (5 mL) was added 6-methylpyridin-3-ol (37 mg, 0.338 mmol), followed by potassium carbonate (58 mg, 0.423 mmol). The reaction was stirred at 80° C. for 2 h. The reaction was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product, which was purified by preparative HPLC to give 7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-8-((6-methylpyridin-3-yl)oxy)-1H-purine-2,6(3H,7H)-dione (110 mg, 80.9% yield) as white solid. 1H-NMR (CD3OD) δ 8.457-8.451(d,1H), 7.776-7.748(d,1H), 7.470-7.374(m, 5H), 5.519(s,2H), 4.291-4.256(t,2H), 3.411(s,3H), 2.584(s,3H), 1.867-1.832(t,2H), 0.618-0.610(m, 2H), 0.403-0.387(m,2H). LCMS retention time 2.619 min; LCMS MH+ 482.

Workup

  1. customThe reaction was partitioned between ethyl acetate and water
  2. washThe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product, which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-02dae47c12be4e7e8ae140bb33d89035
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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