Water → HCID 178441694, Verbindung

HRID 1361905Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1361905
[C:1](=[O:21])([O:17][CH:18](Cl)[CH3:19])[O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]([O:13][N+:14]([O-:16])=[O:15])[CH2:8][O:9][N+:10]([O-:12])=[O:11].[CH2:22]([C:26]1[N:27]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[C:48]3[N:52](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:51]=[N:50][N:49]=3)=[CH:38][CH:37]=2)[C:28]([C:32]([OH:34])=[O:33])=[C:29]([Cl:31])[N:30]=1)[CH2:23][CH2:24][CH3:25].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[CH2:22]([C:26]1[N:27]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[C:48]3[NH:52][N:51]=[N:50][N:49]=3)=[CH:38][CH:37]=2)[C:28]([C:32]([O:34][CH:18]([O:17][C:1]([O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]([O:13][N+:14]([O-:16])=[O:15])[CH2:8][O:9][N+:10]([O-:12])=[O:11])=[O:21])[CH3:19])=[O:33])=[C:29]([Cl:31])[N:30]=1)[CH2:23][CH2:24][CH3:25]

Komponenten

6

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 467832052-Butyl-4-chloro-1-({2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylic acidHCID 59370672(5R)-5,6-bis(nitrooxy)hexyl 1-chloroethyl carbonate

Produkt 1

HCID 178441694HCID 178441694, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

(5R)-5,6-bis(nitrooxy)hexyl 1-chloroethyl carbonate (7.67 g, 23.2 mmol) was added to a stirred solution of 2-butyl-4-chloro-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (6.30 g, 9.3 mmol) and Cs2CO3 (3.02 g, 9.3 mmol) in DMF (186 mL). The solution was stirred at 70° C. for 2 h. Water (50 mL) was added and the solution was extracted with EtOAc (3×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was redissolved in MeOH (186 mL). After stirring at 70° C. for 2 h, the solution was concentrated in vacuo. The residue was purified by HPLC chromatography (50×100 mm C-18) eluting with 40-100% MeCN/water+0.05% TFA. The diastereomers were then separated by HPLC chromatography on silica gel (ChiralPak AD-H) eluting with 20% MeOH in supercritical CO2 to give the title compound as a white solid. 1H NMR (500 MHz, CD3OD) δ 8.06 (d, J=7.5 Hz, 1H), 7.62 (td, J=7.5, 1.0 Hz, 1H), 7.56 (td, J=6.5, 1.0 Hz, 1H), 7.44 (d, J=6.5 Hz, 1H), 7.17 (d, J=8.0 Hz, 2H), 6.99 (d, J=8.0 Hz, 2H), 6.87 (q, J=5.5 Hz, 1H), 5.54 (d, J=6.0 Hz, 2H), 5.24 (ddd, J=13.0, 6.2, 3.0 Hz, 1H), 4.73 (dq, J=12.5, 1.5 Hz, 1H), 4.46 (dd, J=13.0, 6.5 Hz, 1H), 4.14-4.04 (m, 1H), 2.76 (t, J=7.7 Hz, 2H), 1.76-1.59 (m, 6H), 1.61 (d, J=5.5 Hz, 3H) 1.55-1.40 (m, 2H), 1.38 (hex, J=7.5 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H); LCMS (M+H) found 731.1.

Aufarbeitung

  1. extractionthe solution was extracted with EtOAc (3×100 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in MeOH (186 mL)
  6. stirringAfter stirring at 70° C. for 2 h
  7. concentrationthe solution was concentrated in vacuo
  8. customThe residue was purified by HPLC chromatography (50×100 mm C-18)
  9. washeluting with 40-100% MeCN/water+0.05% TFA
  10. customThe diastereomers were then separated by HPLC chromatography on silica gel (ChiralPak AD-H)
  11. washeluting with 20% MeOH in supercritical CO2

Quellen und Nachweise

ORD-Eintrag
ord-f83ed84067114f5f87f6f5701aa99126
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07880014B2

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