Potassium Carbonate → HCID 90402592, compound

HRID 2200700Notes

Reaction equation

HRID 2200700 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)=[CH:4][CH:3]=1.CS([O:37][CH2:38][C:39]1([CH2:42]O)[CH2:41][CH2:40]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:42][C:39]4([CH2:38][OH:37])[CH2:41][CH2:40]4)[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 90403003HCID 90403003, compound2×HCID 90403073HCID 90403073, compound2×

Product 1

HCID 90402592HCID 90402592, compoundYield 39.9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 7-(4-chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (80 mg, 0.17 mmol, intermediate 9) in DMF (5 mL) was added (1-(hydroxymethyl)cyclopropyl)methyl methanesulfonate (0.1 g, 0.5 mmol, intermediate 42), potassium carbonate (47 mg, 0.34 mmol) and TBAI (2 mg, 0.02 mmol). The reaction was stirred at 50° C. for 8 h. The mixture was cooled and partitioned between ethyl acetate and water. The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a crude product which was purified by preparative HPLC to give 7-(4-chlorobenzyl)-1-((1-(hydroxymethyl)cyclopropyl)methyl)-3-methyl-8-(3(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (36 mg, 39.9% yield) as a white solid. 1H-NMR (CD3OD) δ 7.39(t, 1H), 7.01(dd, 1 H), 6.88-6.90(m, 2H), 4.87-4.88(m, 2H), 4.44-4.46(m, 2H), 4.08-4.16(m, 4H), 3.61(t, 2H), 3.51(s, 3H), 1.80-1.90(m, 2H), 1.32(t, 3H). LCMS retention time 3.099 min; LCMS MH+ 533.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned 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 product which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-7e3a9806dc06493e92f0d9524cba3d45
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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