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

HRID 2200690ノート

反応式

HRID 2200690 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-794f5bb4c2564dc080fb3fbdff3394cc
出典データセット
uspto-grants-2016_06
特許番号
US09359359B2

反応ノート

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