Hydrochloric Acid → 5,5'-(5,12-dihydroxy-2,15-dioxo-7,10-dioxa-3,14-diazahexadecane-3,14-diyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)

HRID 41833

Reaktionsgleichung

Reaktionsgleichung von HRID 41833
[OH-:1].[K+].[C:3]([NH:6][C:7]1[C:8]([I:31])=[C:9]([C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:10]([I:22])=[C:11]([C:20]=1[I:21])[C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])(=[O:5])[CH3:4].B(O)(O)O.[O:36]1[CH2:38][CH:37]1[CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH:45]1[CH2:47][O:46]1.Cl>C(#N)C.O.O.CO>[OH:36][CH:37]([CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH:45]([OH:46])[CH2:47][N:6]([C:7]1[C:20]([I:21])=[C:11]([C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])[C:10]([I:22])=[C:9]([C:8]=1[I:31])[C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:3](=[O:1])[CH3:4])[CH2:38][N:6]([C:7]1[C:20]([I:21])=[C:11]([C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])[C:10]([I:22])=[C:9]([C:8]=1[I:31])[C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:3](=[O:5])[CH3:4]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 7628Boric AcidHCID 14797Potassium HydroxideHCID 16683Glycol diglycidyl etherHCID 111153265-Acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Produkt 1

HCID 442189515,5'-(5,12-dihydroxy-2,15-dioxo-7,10-dioxa-3,14-diazahexadecane-3,14-diyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)Ausbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 22242641Methanol--water (1/1)Lösungsmittel

Versuchsvorschrift

To a stirred solution of water/methanol (4.9 ml, 2.5 ml) and potassium hydroxide (0.49 g, 8.7 mmol) at 40° C. was added 5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo isophthalamide (5.0 g, 6.7 mmol). To the clear solution was then added boric acid (0.29 g, 4.6 mmol). The mixture was cooled to room temperature and pH adjusted to 12.6. 2-{[2-(oxiran-2-ylmethoxy)ethoxy]methyl}-oxirane (0.40 g, 2.3 mmol) was added. The pH of the solution was adjusted to the interval 12.6-13. The reaction was left over weekend. To the solution was added HCl (18%) to pH 4. Salts were removed by treatment with ion exchanger AMB200C and IRA67. The solution was filtered from the resin and evaporated. The product was purified by preparative HPLC (column Phenomenex Luna C18(2) 10 μm 250×50.0 mm, solvents: A=water and B=acetonitrile; gradient 05-10% B over 60 min; flow 50.0 ml/min, UV detection at 214 nm and 254 nm), and obtained in 268 mg after lyophilisation, 7% yield. Analysis by LC-MS (column Agilent Zorbax SB-Aq 3.5 μm 3.0×100 mm, solvents: A=water/0.1% formic acid and B=acetonitrile/0.1% formic acid; gradient 0-30% B over 20 min; flow 0.3 ml/min, UV detection at 214 and 254 nm, ESI-MS) gave three isomeric peaks centred at 11.7 minutes with m/z 1668.5 (MH+) corresponding to the structure.

Aufarbeitung

  1. waitThe reaction was left over weekend
  2. customSalts were removed by treatment with ion exchanger AMB200C and IRA67
  3. filtrationThe solution was filtered from the resin
  4. customevaporated
  5. customThe product was purified by preparative HPLC (column Phenomenex Luna C18(2) 10 μm 250×50.0 mm, solvents
  6. customobtained in 268 mg after lyophilisation, 7% yield
  7. waitgradient 0-30% B over 20 min
  8. customgave three isomeric peaks
  9. waitcentred at 11.7 minutes with m/z 1668.5 (MH+) corresponding to the structure

Quellen und Nachweise

ORD-Eintrag
ord-4922a28f56c64fac9498711e745e59c9
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08535642B2

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