Isosorbide Mononitrate → HCID 178467370, 화합물

HRID 222529

반응식

HRID 222529 반응식
[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]

참가 물질

7

반응물 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-carboxylate2회

생성물 1

HCID 178467370HCID 178467370, 화합물

시약·촉매·용매 4

HCID 142844-(Dimethylamino)pyridine촉매HCID 2734571Scandium(III) triflate촉매HCID 887Methanol용매HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-dad1284a7d364a8ea22cd41a1449ff21
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207208B2

연결된 노트

불러오는 중…