5,6-Dichloro-1H-benzimidazole → HCID 70177974, compound

HRID 2227206Notes

Reaction equation

HRID 2227206 reaction equation
[F:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH3:8])[O:4][C@H:3]1N1C=CC(=O)NC1=O.[Cl:17][C:18]1[C:26]([Cl:27])=[CH:25][C:21]2[N:22]=[CH:23][NH:24][C:20]=2[CH:19]=1>C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O>[Cl:27][C:26]1[C:18]([Cl:17])=[CH:19][C:20]2[N:24]([C@@H:3]3[O:4][C@H:5]([CH3:8])[C@@H:6]([OH:7])[C@H:2]3[F:1])[CH:23]=[N:22][C:21]=2[CH:25]=1

Participants

4

Reactant 2

HCID 3317755,6-Dichloro-1H-benzimidazoleHCID 57259416Uridine, 2′,5′-dideoxy-2′-fluoro-

Product 1

HCID 70177974HCID 70177974, compound

Reagents, catalysts & solvents 1

HCID 31348CitrateSolvent

Conditions

Temperature
80 °C

Procedure

2′,5′-Dideoxy-2′-fluorouridine (1.1 g, 4.8 mmoles) was dissolved in 950 mL of 50 mmoler pH 6.0 citrate buffer. 5,6-Dichlorobenzimidazole (Townsend and Revankar, Chem. Rev. 1970, 70:389) (0.53 g, 2.9 mmoles) was added followed by 71,250 units of N-deoxyribofuranosyl transferase (Freeman, et.al, Bioorg. & Med. Chem. 1995, 3(4):447-58). The reaction was placed in a 50° C. water bath and gently shaken for 27 days. The enzyme was precipitated by heating to 80° C. then cooling to room temperature. Celite (50-60 g) was added and the reaction filtered. The product was extracted with ethyl acetate (3×). The ethyl acetate was removed in vacuo and the residue purified by chromatography on 75 g of silica gel eluted with ethyl acetate. The product containing fractions were combined and the solvents removed in vacuo. The yield was 0.5 g, 56%. MS (APCl(+)): m/z, 305; 1H NMR (DMSO-d6) δ8.51 (s, 1H, H-2), 8.03 (s,1H, Ar—H), 7.98 (s,1H, Ar—H), 6.32 (d,1H, H-1′, J=18 Hz), 5.72 (d, 1H, OH-3′, J=6 Hz), 5.34 (d, 1H, H-2′, J=53 Hz), 4.0 (m, 2H,), 1.32 (d, 3H, H-5′, J=4 Hz).

Workup

  1. customwas placed in a 50° C.
  2. customThe enzyme was precipitated
  3. temperaturethen cooling to room temperature
  4. additionCelite (50-60 g) was added
  5. filtrationthe reaction filtered
  6. extractionThe product was extracted with ethyl acetate (3×)
  7. customThe ethyl acetate was removed in vacuo
  8. customthe residue purified by chromatography on 75 g of silica gel
  9. washeluted with ethyl acetate
  10. additionThe product containing fractions
  11. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-7cbc7a22b64f456d9377507460c78bcb
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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