Isosorbide Mononitrate → HCID 178467370, compound

HRID 222529

Reaction equation

HRID 222529 reaction equation
[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]

Participants

7

Reactant 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×

Product 1

HCID 178467370HCID 178467370, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 2734571Scandium(III) triflateCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-dad1284a7d364a8ea22cd41a1449ff21
Source dataset
uspto-grants-2012_06
Patent number
US08207208B2

Linked notes

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