1,1'-(Chlorophenylmethylene)bis(4-methoxybenzene) → 2'-O-Methylcytidine

HRID 2393719Notes

Reaction equation

HRID 2393719 reaction equation
C([NH:4][C:5]1[CH:20]=[CH:19][N:8]([C@@H:9]2[O:18][C@H:15]([CH2:16][OH:17])[C@@H:13]([OH:14])[C@H:10]2[O:11][CH3:12])[C:7](=[O:21])[N:6]=1)(=O)C.COC1C=CC(C(Cl)(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1>N1C=CC=CC=1>[CH3:12][O:11][C@@H:10]1[C@H:13]([OH:14])[C@@H:15]([CH2:16][OH:17])[O:18][C@H:9]1[N:8]1[CH:19]=[CH:20][C:5]([NH2:4])=[N:6][C:7]1=[O:21]

Participants

4

Reactant 2

HCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 10902616Ac-2'-OMe-C

Product 1

HCID 1509712'-O-MethylcytidineYield 65%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In accordance with the present invention, DMT CAc -2'-OMe-3'-cyanoethylphosphoramidite ("CAc 2'-OMe phosphoramidite") of the formula ##STR4## was synthesized as depicted in Scheme I. Cytidine (1) was quantitatively converted to 2 by a selective acetylation procedure [Bhat, U. et al., Nucleoside aid Nucleotides (1989) 8, 179-183)]. N4 -Acetylcytidine 2 was reacted with 1,3-dichloro- 1,1,3,3-tetraisopropyldisiloxane to give N4 -acetyl-3,5'-O-tetraisopropyldisiloxane-1,3-diyl-cytidine (3) in 90% yield. Treatment of 3 with excess MeI/Ag2O [Inoue, H. et al., Nucleic Acids Research (1987) 15, 6131-6148] in dry benzene at room temperature afforded 60% of the 2'-O-methyl derivative (4) after column chromatography. Removal of the silyl groups using Bu4NF in THF at room temperature gave N4 -acetyl-2'-O-methyl cytidine (5) in 42% yield after work up according to literature procedure [Chattopadhyaya, J. et al., Acta Chem. Scand. (1986) B40, 826-830]. The compound 5 was tritylated with 1.2 equivalents of 4,4'-dimethoxytrityl chloride in pyridine at 5° C. for 20 hours to yield the DMT-2'-O-methylcytidine derivative 6 in 65% yield. Phosphorylation of 6 with 2 equivalents of β-cyanoethyl N,N-diisopropylmonochlorophosphoramidite [Sinha, N. D. et al., Nucleic Acids Research (1984) 12, 4539-4537] in tetrahydrofuran in the presence of 4 equivalents of N,N,N-diisopropylethylamine afforded 60% yield of 5'-DMT-N4 -acetyl-2'-O-methylcytidine-3'-phosphoramidite 7. ##STR5##

Workup

  1. customRemoval of the silyl groups
  2. customat room temperature
  3. customgave N4 -acetyl-2'-O-methyl cytidine (5) in 42% yield after work

Sources & evidence

ORD record
ord-b9e1560baba245118a8e8b816f3920cf
Source dataset
uspto-grants-1998_09
Patent number
US05808039

Reaction notes

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