Reacción #417914

Ecuación de reacción

N2

2-cyanoethyl-N,N-diisopropylchlorophosphoramidite

2′-O-benzyl-5′-O-[bis(4-methoxyphenyl)(phenyl)methyl]inosine

N,N-diisopropylethylamine

1-methylimidazole

→

final product

Rendimiento 78.3%

2′-O-benzyl-5′-O-[bis(4-methoxyphenyl)(phenyl)methyl]-3′-O-[(2-cyanoethoxy)(dipropan-2-ylamino)phosphanyl]inosine

Rendimiento 78.3%

Disolventes

methanol

methylene chloride

triethylamine

methanol

methylene chloride

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was then quenched with methanol (5 mL)
2. 2
   workup.STIRRINGstirred for 5 min
3. 3
   OtroAfter the solvent was removed under the reduced pressure
4. 4
   Otrothe residue was purified by flash chromatography (gradient

Procedimiento

Under the protection of N2, 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite (1.21 mL, 5.45 mmol) was added drop-wise to a 0° C. anhydrous tetrahydrofuran (12 mL) solution of 2′-O-benzyl-5′-O-[bis(4-methoxyphenyl)(phenyl)methyl]inosine (1.80 g, 2.72 mmol), N,N-diisopropylethylamine (1.42 mL, 8.17 mmol)), and 1-methylimidazole (0.11 mL, 1.36 mmol). The reaction was gradually warmed to room temperature and stirred for 60 min. The reaction was then quenched with methanol (5 mL) and stirred for 5 min. After the solvent was removed under the reduced pressure, the residue was purified by flash chromatography (gradient: methylene chloride with methanol 0-4%, with 1% triethylamine in both methylene chloride and methanol) to produce 1.83 g (78%, 2.13 mmol) final product. LCMS: for C47H53N6O8P calculated 860.4. found 861.3 [M+H]+ and 884.4 [M+Na]+. 31P NMR (600 MHz, CD3CN) δ: 150.82, 150.55.

Fuente