Reaktion #305086

Reaktionsgleichung

product

Methyl 2-(diphenylphosphino)-4-((6-((E)-3-(1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acrylamido)hexyl)carbamoyl)benzoate

LiOH

product

7-(((11-Azido-3,6,9-trioxaundecyl)oxy)carbamoyl)-4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,9-dicarboxylic acid

→

15

7-(((1-(2-(diphenylphosphoryl)-4-((6-((E)-3-(1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acrylamido)hexyl)carbamoyl)phenyl)-1-oxo-5,8,11-trioxa-2-azatridecan-13-yl)oxy)carbamoyl)-4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,9-dicarboxylic acid

Lösungsmittel

MeCN

water

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe resulting solution was concentrated under a stream of N2 gas for approximately 30 minutes until most of the MeCN
2. 2
   Sonstigehad evaporated which
3. 3
   Sonstigeresulted in a heterogeneous mixture of solid in a red solution
4. 4
   SonstigeThe solid was removed by filtration through a plug of glass wool in a Pasteur pipet
5. 5
   Waschenrinsing with distilled water (0.1 mL)
6. 6
   WaschenThe combined filtrate and rinse
7. 7
   Extraktionwas extracted with EtOAc (3×0.5 mL)
8. 8
   workup.ADDITIONThe red aqueous fraction was treated with a stream of N2 gas for approximately 15 minutes
9. 9
   Sonstigetrace solids were removed by filtration through a plug of glass wool in a Pasteur pipet
10. 10
    Sonstigeto precipitate
11. 11
    SonstigeThe liquor was withdrawn with a pipet
12. 12
    Waschenthe tar was rinsed with distilled water (0.5 mL), which
13. 13
    Sonstigewas also withdrawn with a pipet
14. 14
    workup.DISSOLUTIONThe tar was further dissolved in MeCN—H2O (1:1, 1 mL)
15. 15
    Sonstigethe solution was evaporated in vacuo at room temperature

Vorschrift

The product from EXAMPLE 6 (7, 4.0 mg, 7.3 μMol) was mixed with distilled water (0.4 mL) and treated with 0.5 M LiOH (29 μL, 14.5 μMol). The resulting red solution was diluted with MeCN (0.6 mL). The product from EXAMPLE 12 (14, 25 mg, 33.7 nMol) was added in solid form, then the reaction mixture was placed under an atmosphere of N2 and stirred at room temperature for 48 hours. The reaction mixture was diluted with distilled water (0.4 mL) and the resulting solution was concentrated under a stream of N2 gas for approximately 30 minutes until most of the MeCN had evaporated which resulted in a heterogeneous mixture of solid in a red solution. The solid was removed by filtration through a plug of glass wool in a Pasteur pipet, rinsing with distilled water (0.1 mL). The combined filtrate and rinse was extracted with EtOAc (3×0.5 mL). The red aqueous fraction was treated with a stream of N2 gas for approximately 15 minutes, then trace solids were removed by filtration through a plug of glass wool in a Pasteur pipet. The resulting red solution was acidified by addition of 1N HCl (30 μL, 30 nMol) which caused a dark tar to precipitate and stick to the glass. The liquor was withdrawn with a pipet and the tar was rinsed with distilled water (0.5 mL), which was also withdrawn with a pipet. The tar was further dissolved in MeCN—H2O (1:1, 1 mL) and the solution was evaporated in vacuo at room temperature to afford 15 as a dark orange solid (4 mg, 44%). MS (AP− taken from a MeOH solution) 1278 (M+MeOH-1), 1246 (M−1).

Quelle