Acetic Acid → Maribavir Impurity 57

HRID 1900118

反応式

HRID 1900118 の反応式
[Br:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[C@@H:13]([O:14]C(=O)C)[C@H:8]2[O:9]C(=O)C)[C:5]2[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:4]=2[N:3]=1.CC([O-])=O.[K+].CC(O)=O>CO.O>[C:22]([O:21][CH2:20][C@H:18]1[O:19][C@@H:7]([N:6]2[C:5]3[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:4]=3[N:3]=[C:2]2[Br:1])[C@H:8]([OH:9])[C@@H:13]1[OH:14])(=[O:24])[CH3:23]

参加物

5

反応物 3

HCID 176Acetic AcidHCID 466020[(2R,3R,4R,5R)-3,4-diacetoxy-5-(2-bromo-5,6-dichloro-benzimidazol-1-yl)tetrahydrofuran-2-yl]methyl acetateHCID 517044Potassium Acetate

生成物 1

HCID 22876558Maribavir Impurity 57

試薬・触媒・溶媒 1

HCID 22242641Methanol--water (1/1)溶媒

実験手順

A mixture of 52a (1.048 g, 2.0 mmol) and KOAc (0.98 g, 10.0 mmol) in MeOH/H2O (40 mL/4 mL) was stirred at room temperature for 24 hr. AcOH (0.572 mL, 10.0 mmol) was added and stirring was continued at room temperature for 15 min. The reaction mixture was evaporated and the residue was partitioned between EtOAc/H2O (75 mL/75 mL). The EtOAc layer was washed with sat. NaCl solution (75 mL), dried (Na2SO4), and evaporated. The residue was chromatographed on a silica column (1.9×24 cm, eluted with CHCl3, 2%, 3%, 4% MeOH/CHCl3). Evaporation of fractions 15-27 (15 mL per fraction) and recrystallization from MeOH gave 0.50 g (2 crops, 57%) of 52b as white crystals. MP: 85°-95° C. (melted slowly over a large range) MS: (EI) m/e 437.9398 (15%, M+ =437.9385). 1H NMR (DMSO-d6): d 8.00, 7.95 (2×s, 2, 7-H and 4-H), 5.90 (d, 1, 1'-H, J1'-2' =7.5 Hz), 5.58 (d, 1, 2'-OH, J2'-2'OH =6.5 Hz), 5.46 (d, 1, 3'-OH, J3'-3'OH =4.5 Hz), 4.44 (dd, 1, 5'H, J5'-4' =4.5 Hz, J5'-5" =12.5 Hz), 4.43 (m, 1, 2'-H, J2'-3' =6.0 Hz), 4.24 (dd, 1, 5"-H, J5"-4' =2.0 Hz), 4.16 (m, 1, 4'-H, J3'-4' =3.0 Hz), 4.11 (m, 1, 3'-H), 2.15 (s, 3, 5'-OAc). 13C NMR (DMSO-d6): d 169.96 (COCH3), 142.57 (C3a), 132.49, 132.42 (C2 and C7a), 125.78, 125.74 (C5 and C6), 120.14 (C4), 113.28 (C7), 90.32 (C1'), 82.56 (C4'), 71.27 (C2'), 68.90 (C3'), 63.34 (C5'), 20.58 (COCH3). Anal. Calcd. for C14H13BrCl2N2O5 : C, 38.21; N, 6.37. Found: C, 38.37; H, 2.86; N, 6.27.

後処理

  1. stirringstirring
  2. waitwas continued at room temperature for 15 min
  3. customThe reaction mixture was evaporated
  4. customthe residue was partitioned between EtOAc/H2O (75 mL/75 mL)
  5. washThe EtOAc layer was washed with sat. NaCl solution (75 mL)
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customThe residue was chromatographed on a silica column (1.9×24 cm, eluted with CHCl3, 2%, 3%, 4% MeOH/CHCl3)
  9. customEvaporation of fractions 15-27 (15 mL per fraction) and recrystallization from MeOH

出典と根拠

ORDレコード
ord-d7a7f81e8f7d4012ad64c258e33ec317
出典データセット
uspto-grants-1996_11
特許番号
US05574058

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