Cyclopropylamine → (2R,3R,4S,5R)-2-[5,6-dichloro-2-(cyclopropylamino)benzimidazol-1-yl]-5-methyl-tetrahydrofuran-3,4-diol

HRID 2227223Notes

Reaction equation

HRID 2227223 reaction equation
[Cl:1][C:2]1[C:22]([Cl:23])=[CH:21][C:5]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:7](OC(C)C)=[N:8][C:4]=2[CH:3]=1.[CH:24]1([NH2:27])[CH2:26][CH2:25]1>C1COCC1>[CH:24]1([NH:27][C:7]2[N:6]([C@@H:13]3[O:19][C@H:18]([CH3:20])[C@@H:16]([OH:17])[C@H:14]3[OH:15])[C:5]3[CH:21]=[C:22]([Cl:23])[C:2]([Cl:1])=[CH:3][C:4]=3[N:8]=2)[CH2:26][CH2:25]1

Participants

4

Reactant 2

HCID 69828Cyclopropylamine2×HCID 701790235,6-Dichloro-2-(isopropoxy)-1-(5-deoxy-beta-D-ribofuranosyl)-1H-benzimidazole

Product 1

HCID 9798857(2R,3R,4S,5R)-2-[5,6-dichloro-2-(cyclopropylamino)benzimidazol-1-yl]-5-methyl-tetrahydrofuran-3,4-diolYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5 (0.422 g, 1 mmol) and cyclopropylamine (0.694 mL, 10 mmol) in THF (10 mL) was stirred at room temperature for 18 days (with the addition of 0.694 mL of fresh cyclopropylamine on the 9th day). Volatile materials were removed by evaporation and the residue was treated with NH3/MeOH (15 mL, sat. at 0° C.) at room temperature for 18 h. The reaction mixture was again evaporated and the residue was chromatographed on a silica column (2×15 cm, eluted successively with CHCl3, 4%, 8% MeOH/CHCL3, v/v). Evaporation of fractions 23˜35 (15 mL per fraction) and recrystallization from MeCN gave 0.296 g (83%) of 6 as white crystals. MP: ˜210° C. (dec). HRMS: (EI, with DCI probe) m/z 357.0645 (51%, M+=357.0647). 1H NMR (DMSO-d-6): δ7.48 (s, 1, 4-H), 7.35 (s,1,7-H), 7.14 (d, 1,2′-NH—, J2′NH-1Cp=2 Hz), 5.62 (d, 1,1′-H, J1′-2′=6.5 Hz), 5.26 (d, 1,3′-OH, J3′-3′OH=4.5 Hz), 5.23 (d,1, 2′-OH, J2′-2′OH′=7.0 Hz),4.33 (m, 1,2′-H, J2′-3′=5.5 Hz), 3.90 (m, 1,4′H, J4′-3′=4.5 Hz, J4′-5′=6.5 hz), 3.79 (m, 1, 3′-HO, 2.76 (m, 1,1,-Cp), 1.37 (d, 3,5′-H), 0.71, 0.53 (2×m, 4, 2-Cp and 3-Cp). 13C NMR (DMSO-d-6): δ156.68 (C2), 143.53 (C3a), 132.05 (C7a), 123.27, 120.22 (C5 and C6), 116.38 (C4), 111.05 (C7), 87.56 (C1′), 80.00 (C4′), 73.65 (C3′), 70.85 (C2′), 25.17 (1-Cp), 18.93 (C5″) 6.49, 6.15 (2-Cp and 3-Cp). Anal. Calcd. for C15H17Cl2N3O3: C, 50.29, H, 4.78, N, 11.73. Found C, 50.42, H, 5.00, N, 11.99.

Workup

  1. customVolatile materials were removed by evaporation
  2. additionthe residue was treated with NH3/MeOH (15 mL, sat. at 0° C.) at room temperature for 18 h
  3. customThe reaction mixture was again evaporated
  4. customthe residue was chromatographed on a silica column (2×15 cm
  5. washeluted successively with CHCl3, 4%, 8% MeOH/CHCL3, v/v)
  6. customEvaporation of fractions
  7. custom23˜35 (15 mL per fraction) and recrystallization from MeCN

Sources & evidence

ORD record
ord-a6cecb6ebf124f5998bef7a52d797ba2
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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