Potassium Carbonate → 7-(4-chlorobenzyl)-8-(isopropylsulfonyl)-1-(isoxazol-5-ylmethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

HRID 2200690Notes

Reaction equation

HRID 2200690 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][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[S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[CH:4][CH:3]=1.Cl[CH2:28][C:29]1[O:33][N:32]=[CH:31][CH:30]=1.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]([CH2:28][C:29]4[O:33][N:32]=[CH:31][CH:30]=4)[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[S:19]([CH:22]([CH3:23])[CH3:24])(=[O:20])=[O:21])=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 38580135-(Chloromethyl)isoxazole2×HCID 904030307-(4-chlorobenzyl)-8-(isopropylsulfonyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

Product 1

HCID 904023627-(4-chlorobenzyl)-8-(isopropylsulfonyl)-1-(isoxazol-5-ylmethyl)-3-methyl-1H-purine-2,6(3H,7H)-dioneYield 40.8%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 7-(4-chlorobenzyl)-8-(isopropylsulfonyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (80 mg, 0.20 mmol) in DMF (5 mL) was added 5-(chloromethyl)isoxazole (55 mg, 0.5 mmol, intermediate 41), potassium carbonate (58 mg, 0.42 mmol), and TBAI (2 mg, 0.02 mmol). The reaction was heated at 50° C. overnight. 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)-8-(isopropylsulfonyl)-1-(isoxazol-5-ylmethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (39 mg, 40.6% yield) as a white solid. 1H-NMR (CD3OD) δ 8.49(d, 1H), 7.41(dd, 2 H), 7.28(d, 2H), 6.43(d, 1H), 5.87(s, 2H), 5.21(s, 2H), 3.60-3.73(m, 1H), 3.47(s, 3H), 1.25(d, 6H). LCMS retention time 2.772 min; LCMS MH+ 478

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-794f5bb4c2564dc080fb3fbdff3394cc
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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