Isosorbide Mononitrate → HCID 178467370、化合物

HRID 222529

反応式

HRID 222529 の反応式
[CH2:1]1[O:5][C@@H:4]2[C@H:6]([O:9][N+:10]([O-:12])=[O:11])[CH2:7][O:8][C@@H:3]2[C@H:2]1[OH:13].[CH2:14]([O:16][C:17]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[N:39](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:38]=[N:37][N:36]=3)=[CH:25][CH:24]=2)[C:20]2[C:59]([C:63]([O:65][C:66]([CH3:81])([O:68][C:69](OC3C=CC([N+]([O-])=O)=CC=3)=[O:70])[CH3:67])=[O:64])=[CH:60][CH:61]=[CH:62][C:19]=2[N:18]=1)[CH3:15]>CN(C)C1C=CN=CC=1.ClCCl.CO.FC(F)(F)S([O-])(=O)=O.[Sc+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[CH2:14]([O:16][C:17]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[NH:36][N:37]=[N:38][N:39]=3)=[CH:25][CH:24]=2)[C:20]2[C:59]([C:63]([O:65][C:66]([O:68][C:69]([O:13][C@H:2]3[CH2:1][O:5][CH:4]4[C@H:6]([O:9][N+:10]([O-:12])=[O:11])[CH2:7][O:8][CH:3]34)=[O:70])([CH3:81])[CH3:67])=[O:64])=[CH:60][CH:61]=[CH:62][C:19]=2[N:18]=1)[CH3:15]

参加物

7

反応物 2

HCID 27661Isosorbide MononitrateHCID 597787481-methyl-1-{[(4-nitrophenoxy)carbonyl]oxy}ethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate2 回

生成物 1

HCID 178467370HCID 178467370、化合物

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 2734571Scandium(III) triflate触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

Isosorbide-5-mononitrate (0.203 g, 1.06 mmol) was added to a stirred solution of 1-methyl-1-{[(4-nitrophenoxy)carbonyl]oxy}ethyl 2-ethoxy-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate (Intermediate 1, 0.800 g, 0.883 mmol), 4-dimethylaminopyridine (0.162 g, 1.33 mmol) and scandium trifluoromethanesulfonate (0.087 g; 0.177 mmol) in dichloromethane (12 mL). The solution was stirred at room temperature for 24 hours. Then the mixture was diluted with dichloromethane, washed with aqueous sodium dihydrogenphosphate (20 mL) and brine (20 mL); the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (Biotage SP1; column 40+M; TLC method: n-hexane/ethyl acetate: 6/4; Rf=0.33) to afford a solid that was dissolved in methanol (8 mL). The mixture was stirred at 40° C. for 5 hours, at 60° C. for 2 hours, and at room temperature for 18 hours. Then the solution was concentrated under reduced pressure. The residue was purified by flash chromatography (Biotage SP1; column 25+M; dichloromethane/methanol: 98/2), affording the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.03 (d, 1H), 7.69-7.58 (m, 2H), 7.48 (d, 1H), 7.31 (d, 1H), 6.88 (t, 1H), 6.80 (d, 2H), 6.76-6.62 (m, 3H), 5.60 (s, 2H), 5.41-5.33 (m, 1H), 5.03 (d, 1H), 4.95 (t, 1H), 4.48 (d, 1H), 4.36-4.15 (m, 2H), 4.10-3.86 (m, 3H), 1.62 (d, 6H) 1.43 (t, 3H).

後処理

  1. washwashed with aqueous sodium dihydrogenphosphate (20 mL) and brine (20 mL)
  2. dry with materialthe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (Biotage SP1; column 40+M; TLC method: n-hexane/ethyl acetate: 6/4; Rf=0.33)
  5. customto afford a solid
  6. stirringThe mixture was stirred at 40° C. for 5 hours, at 60° C. for 2 hours
  7. waitat room temperature for 18 hours
  8. concentrationThen the solution was concentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (Biotage SP1; column 25+M; dichloromethane/methanol: 98/2)

出典と根拠

ORDレコード
ord-dad1284a7d364a8ea22cd41a1449ff21
出典データセット
uspto-grants-2012_06
特許番号
US08207208B2

関連ノート

読み込み中…