Water → 2-Amino-6-methoxy-9-(5-O-propionyl-beta-D-arabinofuranosyl)-9H-purine

HRID 1288795

反応式

HRID 1288795 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@@H:12]2[OH:13])=[C:4]([O:20][CH3:21])[N:3]=1.O.[C:23](OCC(Cl)(Cl)Cl)(=[O:26])[CH2:24][CH3:25]>N1C=CC=CC=1>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][O:19][C:23](=[O:26])[CH2:24][CH3:25])[C@@H:14]([OH:15])[C@@H:12]2[OH:13])=[C:4]([O:20][CH3:21])[N:3]=1

参加物

5

反応物 3

HCID 962WaterHCID 5271512,2,2-Trichloroethyl propionateHCID 3011155Nelarabine

生成物 1

HCID 536401282-Amino-6-methoxy-9-(5-O-propionyl-beta-D-arabinofuranosyl)-9H-purine

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
40 °C

実験手順

2-Amino-6-methoxy-9-(β-D-arabinofuranosyl)-9H-purine (1.0 g, 3.3 mmol) (prepared as described in European Patent Application No. 294 114) was suspended in 40 ml of pyridine that contained 300 μL of H2O and 2 ml of trichloroethyl propionate (Trichloroethyl propionate was synthesized by addition of 19 ml of propionyl chloride (Aldrich) over 30 minutes to 19.1 ml of trichlorethanol (Aldrich) in 40 ml of pyridine at 0° C.). The product was purified by successive washing with 2×100 ml aliquots of H2O, 5% NaHCO3, and H2O. 1H NMR (200 MHz, CDCl3 , 4.74 (s, 2H, Cl3CH2-), 2.49 (q, 2H, J=7.6 Hz, CH3CH2CO2-), 1.21 (t, 3H, J=7.6 Hz, CH3CH2 CO2-). The reaction was initiated with 0.100 g of subtilisin (Sigma Chemical Co., St. Louis, Mo., P-5380, lot No. 38F-0356), whch had been activated by dissolving 1 g of the enzyme in 20 ml of 0.1M potassium phosphate at pH 7.8 and lyophilizing to dryness. After stirring for 23 hours at 40° C., the reaction was quenched by filtering off the enzyme and the solvent was removed in vacuo. The crude product was purified by chromatography on a 4.5×25 cm silica gel column with CH2Cl2 :CH3OH (9:1) as eluant. Product fractions were pooled and lyophilized from water to yield 0.76 g of the desired product as a white powder: m.p. 124° C.; TLC Rf =0.43 (silica gel; CH1Cl2 :CH3OH (9:1)); UV λmax (ε, mM-1 cm-1) at pH 7.0, 278 nm (9.5). 1H NMR (200 MHz, DMSO-d6), δ 7.83(s, 1H, H8, 6.44 (s, 2H, 2-NH2), 6.14 (s, 1H, H1'), 5.75 (d, 1H, J=4.3 Hz, 2'-OH), 5.65 (d, 1H, J=3.5 Hz, 3'-OH), 4.28 (m, 2H, H2' and H3'), 4.08 (m, 2H, H5'), 3.95 (s, 3H, --OCH3), 3.91 (m, 1H, H4 '), 2.32 (q, 2H, J=7.6 Hz, CH3CH2CO2-), 1.01 (t, 3H, J=7.5 Hz, CH3CH2 CO2-); MS (ci) 354 (M+1), 280 (M--C2H5CO2). Anal. Calcd. for C14H19N5O6.0.46 H2O: Calcd: C, 46.49; H, 5.55; N, 19.36 Found: C, 46.46; H, 5.52; N. 19.45.

後処理

  1. customThe product was purified
  2. washby successive washing with 2×100 ml aliquots of H2O, 5% NaHCO3, and H2O
  3. dissolutionby dissolving 1 g of the enzyme in 20 ml of 0.1M potassium phosphate at pH 7.8
  4. customthe reaction was quenched
  5. filtrationby filtering off the enzyme
  6. customthe solvent was removed in vacuo
  7. customThe crude product was purified by chromatography on a 4.5×25 cm silica gel column with CH2Cl2 :CH3OH (9:1) as eluant

出典と根拠

ORDレコード
ord-059e5a9793b94470809c54ea079e1b85
出典データセット
uspto-grants-1998_05
特許番号
US05747472

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