تفاعل #218746

معادلة التفاعل

hydrazine

Potassium carbonate

product

6-[(4,5-Dichloro-2-methyl-1H-imidazol-1-yl)methyl]-5-[4-(S)-hydroxy-2-isoxazolidinylcarbonyl]-3-methyl-1-(isobutyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

2,4-pentanedione

→

sub-title compound

6-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylic acid

المذيبات

water

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   استخلاصextracted with ethyl acetate (2×60 ml)
2. 2
   تجفيفOrganic extracts were dried over anhydrous magnesium sulfate
3. 3
   ترشيحfiltered
4. 4
   أخرىevaporated under reduced pressure
5. 5
   أخرىThe residue was purified by column chromatography over silica
6. 6
   غسيلeluting with ethyl acetate
7. 7
   workup.DISSOLUTIONThe product was dissolved in tetrahydrofuran (20 ml)
8. 8
   workup.ADDITIONmethanol (3 ml) then treated with sodium hydroxide solution (1M, 2.57 ml)
9. 9
   workup.WAITAfter 3 days
10. 10
    أخرىthe mixture was evaporated under reduced pressure to ca. 5 ml
11. 11
    workup.ADDITIONdiluted with water (25 ml)
12. 12
    استخلاصextracted with ethyl acetate (25 ml)
13. 13
    استخلاصextracted with ethyl acetate (3×25 ml)
14. 14
    تجفيفOrganic extracts were dried over anhydrous magnesium sulfate
15. 15
    ترشيحfiltered
16. 16
    أخرىevaporated under reduced pressure

الإجراء التجريبي

Potassium carbonate (3.55 g) and dichlorobis(triphenylphosphine)cobalt(II) (0.1 g) were added to a stirred solution of the product of example 3, part a) (1 g) and 2,4-pentanedione (2.64 ml) in dichloromethane (30 ml) under nitrogen. After 48 h, aqueous hydrazine (35%, 2.33 ml) was added and the mixture stirred vigorously for 1 h, diluted with water (30 ml) and extracted with ethyl acetate (2×60 ml). Organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with ethyl acetate. The product was dissolved in tetrahydrofuran (20 ml) and methanol (3 ml) then treated with sodium hydroxide solution (1M, 2.57 ml). After 3 days, the mixture was evaporated under reduced pressure to ca. 5 ml, diluted with water (25 ml) and extracted with ethyl acetate (25 ml). The aqueous phase was acidified with hydrochloric acid and extracted with ethyl acetate (3×25 ml). Organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to give the sub-title compound as a solid (0.23 g). MS(ESI) 391 [M+H]+. δ 1HDMSO 0.85 (6H, d), 2.05-2.18 (1H, m), 2.08 (6H, s), 3.17 (3H, s), 3.62 (2H, d), 3.71 (2H, s).

المصدر