반응 #70112

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2-{[2-(oxiran-2-ylmethoxy)-ethoxy]methyl}oxirane

potassium hydroxide

5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-N,N′-dimethyl isophthalamide

HCl

boric 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-triiodo-N1,N3-dimethylisophthalamide)

수율 5.0%

용매

acetonitrile

water

water methanol

반응 조건

후처리

1. 1
   workup.WAITThe reaction was left over weekend
2. 2
   기타Salts were removed by treatment with ion exchanger AMB200C and IRA67
3. 3
   여과The solution was filtered from the resin
4. 4
   기타evaporated
5. 5
   기타The product was purified by preparative HPLC (column YMC amino 21.2×250 mm, solvents
6. 6
   기타obtained in 180 mg after lyophilisation, 5% yield
7. 7
   workup.WAITgradient 0-30% B over 20 min
8. 8
   기타gave one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure

실험 절차

To a stirred solution of water/methanol (4.9 ml, 2.5 ml) and potassium hydroxide (0.47 g, 8.4 mmol) at 40° C. was added 5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-N,N′-dimethyl isophthalamide (5.0 g, 6.5 mmol). To the clear solution was then added boric acid (0.28 g, 4.5 mmol). The mixture was cooled to room temperature and pH adjusted to 12.6. 2-{[2-(oxiran-2-ylmethoxy)-ethoxy]methyl}oxirane (0.382 g, 2.22 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 YMC amino 21.2×250 mm, solvents: A=water and B=acetonitrile; gradient 85-65% B over 25 min; flow 25.0 ml/min, UV detection at 214 nm and 254 nm), and obtained in 180 mg after lyophilisation, 5% 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 one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure.

출처