Potassium Carbonate → 7-(4-chlorobenzyl)-3-methyl-8-(6-methylpyridin-3-yloxy)-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione

HRID 2200681Notes

Reaction equation

HRID 2200681 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][CH2:22][O:23][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)[C:6](=[O:30])[N:5]([CH3:31])[C:4]=2[N:3]=1.[CH3:32][C:33]1[N:38]=[CH:37][C:36]([OH:39])=[CH:35][CH:34]=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][CH2:22][O:23][CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[C:6](=[O:30])[N:5]([CH3:31])[C:4]=3[N:3]=[C:2]2[O:39][C:36]2[CH:37]=[N:38][C:33]([CH3:32])=[CH:34][CH:35]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 142752-Methyl-5-hydroxypyridineHCID 904026828-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione2×

Product 1

HCID 904029507-(4-chlorobenzyl)-3-methyl-8-(6-methylpyridin-3-yloxy)-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dioneYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 8-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (100 mg, 0.195 mmol, intermediate 14) in DMF (5 mL) was added 6-methylpyridin-3-ol (24 mg, 0.22 mmol) followed by potassium carbonate (76 mg, 0.55 mmol) and the mixture was stirred at 85° C. for 3 h. The mixture was cooled and partitioned between ethyl acetate and brine. The layers were separated and the organic layer was washed with saturated aqueous ammonium chloride, dried and concentrated to give 7-(4-chlorobenzyl)-3-methyl-8-(6-methylpyridin-3-yloxy)-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (79 mg, 75% yield) as yellow solid. LCMS retention time 2.297 min; LCMS MH+-THP 456.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and brine
  3. customThe layers were separated
  4. washthe organic layer was washed with saturated aqueous ammonium chloride
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1d158315742b4a0abcc2b728f127d292
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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