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

HRID 2200690노트

반응식

HRID 2200690 반응식
[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

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 38580135-(Chloromethyl)isoxazole2회HCID 904030307-(4-chlorobenzyl)-8-(isopropylsulfonyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매

반응 조건

온도
50 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-794f5bb4c2564dc080fb3fbdff3394cc
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359359B2

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