Potassium Carbonate → 7-benzyl-3-ethyl-1-(isoxazol-5-ylmethyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200673ノート

反応式

HRID 2200673 の反応式
[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[N:12]([CH2:19][CH3:20])[C:11]=2[N:10]=[C:9]1[O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:32])([F:31])[F:30])[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:34][C:35]1[O:39][N:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[N:14]([CH2:34][C:35]3[O:39][N:38]=[CH:37][CH:36]=3)[C:13](=[O:18])[N:12]([CH2:19][CH3:20])[C:11]=2[N:10]=[C:9]1[O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:31])([F:30])[F:32])[CH:23]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 38580135-(Chloromethyl)isoxazoleHCID 904027047-benzyl-3-ethyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione2 回

生成物 1

HCID 904031437-benzyl-3-ethyl-1-(isoxazol-5-ylmethyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione収率 12.6%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution of 7-benzyl-3-ethyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (40 mg, 0.090 mmol, intermediate 47) in DMF (3 mL) was added 5-(chloromethyl)isoxazole (30 mg, 0.256 mmol), followed by potassium carbonate (50 mg, 0.362 mmol) and TBAI (5 mg, 0.014 mmol). The reaction was stirred at 60° C. overnight. The mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, and concentrated to give a crude product, which was purified by preparative HPLC to give 7-benzyl-3-ethyl-1-(isoxazol-5-ylmethyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (5.9 mg, 12.6% yield) as white solid. 1H-NMR (CD3OD) δ 8.33-8.32(d, 1H), 7.57-7.53(t, 1H), 7.47-7.45(d, 2H), 7.38-7.31(m, 5H), 7.25-7.23(d, 1H), 6.34-6.33(dd, 1H), 5.52(s, 2H), 5.36(s, 2H), 4.06-4.01(q, 2H), 1.27-1.24(t, 3H). LCMS retention time 3.269 min; LCMS MH+528.

後処理

  1. temperatureThe mixture 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. 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-d3216b0d1f804fa8a9c0f4a290839641
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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