Potassium Carbonate → HCID 90402512, compound

HRID 2200709Notes

Reaction equation

HRID 2200709 reaction equation
[OH:1][C:2]1([CH2:5][CH2:6][N:7]2[C:15](=[O:16])[C:14]3[NH:13][C:12]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=4)=[N:11][C:10]=3[N:9]([CH3:29])[C:8]2=[O:30])[CH2:4][CH2:3]1.Cl.Cl[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][N:35]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[OH:1][C:2]1([CH2:5][CH2:6][N:7]2[C:15](=[O:16])[C:14]3[N:13]([CH2:33][C:34]4[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][N:35]=4)[C:12]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:26])([F:27])[F:28])[CH:19]=4)=[N:11][C:10]=3[N:9]([CH3:29])[C:8]2=[O:30])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 233137952-(Chloromethyl)-5-methylpyridine hydrochloride2×HCID 90402765HCID 90402765, compound2×

Product 1

HCID 90402512HCID 90402512, compoundYield 33.8%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (50 mg, 0.117 mmol, intermediate 58) in DMF (3 mL) was added 2-(chloromethyl)-5-methylpyridine hydrochloride (24.9 mg, 0.176 mmol, intermediate 50), followed by potassium carbonate (48.6 mg, 0.351 mmol) and TBAI (10 mg, 0.027 mmol). The reaction was stirred at 65° C. overnight. The reaction was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give crude product, which was purified by preparative HPLC to give 1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-7-((5-methylpyridin-2-yl)methyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (21 mg, 33.7% yield) as white solid.

Workup

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

Sources & evidence

ORD record
ord-cd289047ec4f42b29364812500623142
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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