Sodium hydride → 7-(4-chlorobenzyl)-3-methyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-8-(3-(3-(trifluoromethoxy)phenoxy)propoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200667Notes

Reaction equation

HRID 2200667 reaction equation
[F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:5]=[C:6]([CH:12]=[CH:13][CH:14]=1)[O:7][CH2:8][CH2:9][CH2:10][OH:11].[H-].[Na+].Br[C:20]1[N:28]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)[C:27]2[C:26](=[O:37])[N:25]([CH2:38][CH2:39][O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)[C:24](=[O:47])[N:23]([CH3:48])[C:22]=2[N:21]=1.[Cl-].[NH4+]>C1COCC1>[Cl:36][C:33]1[CH:32]=[CH:31][C:30]([CH2:29][N:28]2[C:27]3[C:26](=[O:37])[N:25]([CH2:38][CH2:39][O:40][CH:41]4[CH2:46][CH2:45][CH2:44][CH2:43][O:42]4)[C:24](=[O:47])[N:23]([CH3:48])[C:22]=3[N:21]=[C:20]2[O:11][CH2:10][CH2:9][CH2:8][O:7][C:6]2[CH:12]=[CH:13][CH:14]=[C:4]([O:3][C:2]([F:15])([F:16])[F:1])[CH:5]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 672754643-(3-(Trifluoromethoxy)phenoxy)propan-1-ol2×HCID 904028838-bromo-7-(4-chlorobenzyl)-3-methyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-purine-2,6(3H,7H)-dione2×

Product 1

HCID 904033007-(4-chlorobenzyl)-3-methyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-8-(3-(3-(trifluoromethoxy)phenoxy)propoxy)-1H-purine-2,6(3H,7H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(3-(trifluoromethoxy)phenoxy)propan-1-ol (95 mg, 0.4 mmol, intermediate 35) in THF (5 mL) was added sodium hydride (19 mg, 0.40 mmol) at 0° C. After stirred at 0° C. for 30 min, 8-bromo-7-(4-chlorobenzyl)-3-methyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-purine-2,6(3H,7H)-dione (0.1 g, 0.20 mmol, intermediate 13) was added. The mixture was allowed to warm to room temperature and stirred for 16 h. Then the reaction was chilled to 0° C. and aqueous ammonium chloride solution (2 mL) was added. The mixture was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated to give crude product which was used without purification. LCMS MH+-THP 569.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 16 h
  3. temperatureThen the reaction was chilled to 0° C.
  4. customThe mixture was partitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude product which
  9. customwas used without purification

Sources & evidence

ORD record
ord-3220dd20566b41e48294278f9c90de46
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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