Water → 2,5,6-Trichloro-3-[n-(acetylamino)iminomethylidene]-1-(beta-d-ribofuranosyl)indole

HRID 28353

Reaction equation

HRID 28353 reaction equation
[Cl:1][C:2]1[N:3]([C@@H:15]2[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]2[OH:17])[C:4]2[C:9]([C:10]=1[CH:11]=O)=[CH:8][C:7]([Cl:13])=[C:6]([Cl:14])[CH:5]=2.[CH3:24][C:25]([NH:27][NH2:28])=[O:26].O>CO>[Cl:1][CH:2]1[C:10](=[C:11]=[N:28][NH:27][C:25](=[O:26])[CH3:24])[C:9]2[C:4](=[CH:5][C:6]([Cl:14])=[C:7]([Cl:13])[CH:8]=2)[N:3]1[C@@H:15]1[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]1[OH:17]

Participants

5

Reactant 3

HCID 962WaterHCID 14039AcetohydrazideHCID 3011610Ftcri

Product 1

HCID 872686932,5,6-Trichloro-3-[n-(acetylamino)iminomethylidene]-1-(beta-d-ribofuranosyl)indoleYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2,5,6-Trichloro-3-formyl-1-(β-D-ribofuranosyl)indole (4.3, 109 mg, 0.29 mmol) was dissolved in MeOH (5 mL) to which was added acethydrazine (85 mg, 1.1 mmol). The resulting solution was heated on a 45 C oil bath for 16 h, then cooled to room temperature and poured into 15 mL of water. The resulting suspension was cooled to 4C, then filtered and the solids rinsed with cold water (25 mL). The solids were dissolved in DMF (0.5 mL) and subjected to column chromatography (40×350 mm) on C18-reverse phase silica gel with 75% MeOH/H2O. Fractions containing product were pooled and evaporated to yield a white crystalline solid, which was recrystallized from acetone/MeOH to yield 70 mg (56%) of 4.32 as a white microcrystalline solid which is an inseparable mixture of isomers in a ratio of 60:40: mp 270-271 C; Rf 0.2 (10% MeOH/CHCI3); 1H-NMR (500 MHz, DMSO-d6): (major isomer) δ 11.25 (s, 1H, D2O exch.), 8.56 (s, 1H), 8.27 (s, 1H), 8.18 (s, 1H), 5.94 (d, 1H), 5.40-5.36 (m, 2H, D2O exch.), 5.25 (d, 1H, D2O exch.), 4.42 (q, 1H), 4.13 (s, 1H), 3.98 (s, 1H), 3.70(s, 2H), 2.24 (s, 3H); (minor isomer) δ 11.41 (s, 1H, D2O exch.), 8.56 (s, 1H), 8.44 (s, 1H), 8.32 (s, 1H), 5.94 (d, 1H), 5.40-5.36 (m, 2H, D2O exch.), 5.25 (d, 1H, D2O exch.), 4.42 (q, 1H), 4.13 (s, 1H), 3.98 (s, 1H), 3.70(s, 2H), 1.95 (s, 3H). 13C-NMR (125 MHz, DMSO-d6): (major isomer) δ 171.39, 135.98, 133.15, 129.73, 126.01, 124.96, 123.86, 121.69, 115.41, 108.31, 88.78, 86.09, 71.41, 69.66, 61.10, 20.36; (minor isomer) δ 165.24, 138.70, 133.12, 129.82, 126.06, 124.96, 123.99, 122.17, 115.33, 108.51, 88.78, 86.09, 71.41, 69.66, 61.10, 21.67. HRMS (ES) m/z calcd. for C16H16Cl3N3O5·Na 458.0053, found 458.0043. Anal calcd for C16H16Cl3N3O5: C, 44.01; H, 3.69; N, 9.62. Found: C, 43.76; H, 3.75; N, 9.67.

Workup

  1. temperatureThe resulting solution was heated on a 45 C oil bath for 16 h
  2. filtrationfiltered
  3. washthe solids rinsed with cold water (25 mL)
  4. dissolutionThe solids were dissolved in DMF (0.5 mL)
  5. additionFractions containing product
  6. customevaporated
  7. customto yield a white crystalline solid, which
  8. customwas recrystallized from acetone/MeOH

Sources & evidence

ORD record
ord-61aad179bf0f41f7a5d5227aa2625494
Source dataset
uspto-grants-2008_09
Patent number
US07419963B2

Linked notes

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