Reaktion #483449

Reaktionsgleichung

nonaethyleneglycol(4-carboxybenzyl)methyl ether

( a )

Nonaethyleneglycol(4-carboxybenzyl)methyl ether

oxalyl chloride

triethylamine

1,3-bis(cyclohexylmethyl)-5,6-diaminouracil

( a )

Nonaethyleneglycol(4-carboxybenzyl)methyl ether

→

1,3-Bis(cyclohexylmethyl)-8-[4-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1H-purine-2,6-dione

Lösungsmittel

dichloromethane

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe volatiles were removed in vacuo
2. 2
   Sonstigeto give a tan oil
3. 3
   workup.STIRRINGto stir at room temperature for 18 hours
4. 4
   Sonstigethe volatiles were removed in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in ethanol (25 ml)
6. 6
   workup.ADDITIONthe pH was adjusted to ˜13 by addition of 2N sodium hydroxide
7. 7
   workup.STIRRINGto stir
8. 8
   Temperaturat reflux for 0.5 hours
9. 9
   workup.ADDITIONChloroform (100 ml) was added
10. 10
    Waschenthe solution was washed with 1N hydrochloric acid (50 ml), saturated aqueous sodium chloride (20 ml)
11. 11
    Trocknendried over magnesium sulfate
12. 12
    Filtrationfiltered
13. 13
    SonstigeThe volatiles were removed in vacuo
14. 14
    Waschenthe title compound was eluted from silica gel with 15% methanol-ethyl acetate as a tan waxy solid after solidification from ethyl acetate-hexanes (0.098 g, 14%)

Vorschrift

To a solution of nonaethyleneglycol(4-carboxybenzyl)methyl ether (0.45 g, 0.80 mmol) from Example 97 part (a) above, in dichloromethane (15 ml) was added oxalyl chloride (Fluka, 0.14 ml, 1.6 mmol) and N,N dimethylformamide (one drop). This solution was allowed to stir for 0.5 hours and the volatiles were removed in vacuo to give a tan oil. This material was dissolved in dichloromethane (20 ml) and a solution of triethylamine (0.5 ml, 3.8 mmol) and 1,3-bis(cyclohexylmethyl)-5,6-diaminouracil from Example 21, part (a), (0.270 g, 0.80 mmol) in dichloromethane (10 ml) were added. This solution was allowed to stir at room temperature for 18 hours and the volatiles were removed in vacuo. The residue was dissolved in ethanol (25 ml) and the pH was adjusted to ˜13 by addition of 2N sodium hydroxide. The solution was allowed to stir at reflux for 0.5 hours and then cooled to room temperature. Chloroform (100 ml) was added and the solution was washed with 1N hydrochloric acid (50 ml), saturated aqueous sodium chloride (20 ml), dried over magnesium sulfate and filtered. The volatiles were removed in vacuo and the title compound was eluted from silica gel with 15% methanol-ethyl acetate as a tan waxy solid after solidification from ethyl acetate-hexanes (0.098 g, 14%). 1H-NMR (300 MHz, DMSO-d6) δ: 8.07 (d, J=8.2 Hz, 2H , phenylCH), 7.44 (d, J=8.1 Hz, 2H, phenylCH), 4.54 (s, 2H, CH2—phenyl), 3.89 (d, J=7.2 Hz, 2H, CH2N), 3.70 (d, J=7.2 Hz, 2H, CH2N ), 3.60-3.35 (m, 36H, 18CH2), 3.20 (s, 3H, CH3), 2.05-1.50 and 1.30-0.95 (m, 22H, cyclohexyl CH2's).

Quelle