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

HRID 2200678Notes

Reaction equation

HRID 2200678 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[C:10]1[N:18]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[C:17]2[C:16](=[O:27])[N:15]([CH2:28][CH2:29][CH2:30][O:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[C:14](=[O:38])[N:13]([CH3:39])[C:12]=2[N:11]=1.[Cl-].[NH4+]>C1COCC1>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:18]2[C:17]3[C:16](=[O:27])[N:15]([CH2:28][CH2:29][CH2:30][O:31][CH:32]4[CH2:37][CH2:36][CH2:35][CH2:34][O:33]4)[C:14](=[O:38])[N:13]([CH3:39])[C:12]=3[N:11]=[C:10]2[O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 7298CyclopentanolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 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 904027387-(4-chlorobenzyl)-8-(cyclopentyloxy)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dioneYield 89.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of cyclopentanol (67 mg, 0.78 mmol) in THF (5 mL) was added sodium hydride (39 mg, 0.98 mmol) at 0° C. After stirring at 0° C. for 30 min, 8-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (0.2 g, 0.39 mmol, intermediate 14) was added. The mixture was stirred at room temperature for 16 h; then aqueous ammonium chloride solution (2 mL) was added at 0° C. The reaction mixture was partitioned between ethyl acetate and water. The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a crude solid product. This material was slurried in ice cold ethanol, collected by filtration, and dried under vacuum to give 7-(4-chlorobenzyl)-8-(cyclopentyloxy)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (180 mg, 89.5% yield) as white solid. LCMS retention time 2.085 min; LCMS MH+-THP 433.

Workup

  1. stirringThe mixture was stirred at room temperature for 16 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude solid product
  7. filtrationcollected by filtration
  8. customdried under vacuum

Sources & evidence

ORD record
ord-0ab8e2fa49764cfd8f30b406554a6bd6
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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