Ethylamine → 5,6-dichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-(methylamino)indole-3-carbaldehyde

HRID 28346

反応式

HRID 28346 の反応式
Cl[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:12])=[CH:8][C:7]([Cl:13])=[C:6]([Cl:14])[CH:5]=2.CO.C(Cl)(Cl)Cl.CO.O.[CH2:33]([NH2:35])C>C(O)C.CO>[Cl:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[Cl:14])[N:3]([C@@H:15]1[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]1[OH:17])[C:2]([NH:35][CH3:33])=[C:10]2[CH:11]=[O:12]

参加物

7

反応物 4

HCID 6341EthylamineHCID 3011610FtcriHCID 21584188Chloroform methanolHCID 22242641Methanol--water (1/1)

生成物 1

HCID 115163165,6-dichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-(methylamino)indole-3-carbaldehyde収率 43%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 887Methanol溶媒2 回

実験手順

2,5,6-Trichloro-3-formyl-1-(β-D-ribofuranosyl)indole (4.3, 125 mg, 0.33 mmol) was dissolved in 33% ethylamine solution in ethanol (10 mL), and the resulting solution was stirred at room temperature for 30 min. The solvent was then evaporated to approx 1 mL, and diluted with EtOAc (50 mL). The suspension was washed with H2O (20 mL) and brine (50 mL), then dried over MgSO4, filtered and evaporated to yield a yellow residue. The residue was dissolved in MeOH (1 mL) and subjected to column chromatography (40×350 mm) on silica gel with 20% MeOH/CHCl3. Fractions containing product were pooled and evaporated to yield a clear viscous residue which was dissolved in MeOH (1 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 solid which was recrystallized from MeOH/H2O to yield 56 mg (43%) of 4.18 as a white microcrystalline solid: mp 241-242 C; Rf 0.5 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.98 (s, 1H), 8.24 (s, 1H), 7.97 (q, 1H, D2O exch.), 7.69 (s, 1H), 5.93 (t, 1H, D2O exch.), 5.91 (d, 1H), 5.34 (d, 1H, D2O exch.), 5.32 (d, 1H, D2O exch.), 4.34 (q, 1H), 4.09 (t, 1H), 4.05 (s, 1H), 3.76-3.67 (m, 2H), 3.12 (d, 3H). 13C-NMR (125 MHz, DMSO-d6): δ 181.72, 154.48, 133.66, 127.05, 123.71, 122.72, 119.70, 110.91, 100.20, 88.56, 86.10, 70.78, 70.30, 60.80, 33.45. HRMS (ES) m/z calcd. for C15H16Cl2N2O5+H 375.0514, found 375.0511. Anal calcd for C15H16Cl2N2O5 ¼H2O: C, 47.45; H, 4.38; N, 7.38. Found: C, 47.53; H, 4.59; N, 7.26.

後処理

  1. customThe solvent was then evaporated to approx 1 mL
  2. additiondiluted with EtOAc (50 mL)
  3. washThe suspension was washed with H2O (20 mL) and brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a yellow residue
  8. additionFractions containing product
  9. customevaporated
  10. customto yield a clear viscous residue which
  11. additionFractions containing product
  12. customevaporated
  13. customto yield a white solid which
  14. customwas recrystallized from MeOH/H2O

出典と根拠

ORDレコード
ord-299fb32ce81e4517bbaf4a96682e71e5
出典データセット
uspto-grants-2008_09
特許番号
US07419963B2

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