Water → 4-(morpholin-4-yl)-5-[3-(1,2,4-oxadiazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 1750302ノート

反応式

HRID 1750302 の反応式
[CH:1](OCC)(OCC)OCC.B(F)(F)F.CCOCC.[OH:20][N:21]=[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[C:38]3[C:37]([N:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[N:36][CH:35]=[N:34][C:33]=3[N:32](COCC[Si](C)(C)C)[CH:31]=2)[CH:25]=1)[NH2:23].O>O1CCCC1>[N:39]1([C:37]2[C:38]3[C:30]([C:26]4[CH:27]=[CH:28][CH:29]=[C:24]([C:22]5[N:23]=[CH:1][O:20][N:21]=5)[CH:25]=4)=[CH:31][NH:32][C:33]=3[N:34]=[CH:35][N:36]=2)[CH2:40][CH2:41][O:42][CH2:43][CH2:44]1

参加物

6

反応物 4

HCID 962WaterHCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 86706972HCID 86706972、化合物

生成物 1

HCID 867069734-(morpholin-4-yl)-5-[3-(1,2,4-oxadiazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
40 °C

実験手順

Triethyl orthoformate (760 mg, 5.1 mol) and boron trifluoride diethyl etherate (370 mg, 2.6 mol) were added to a 0° C. solution of N′-hydroxy-3-[4-(morpholin-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzenecarboximidamide (C35) (600 mg, 1.3 mmol) in tetrahydrofuran (25 mL). The reaction mixture was heated at 40° C. for 18 hours, then poured into water (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated. Purification via preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 30% to 50% B) provided the product as a yellow solid. Yield: 62 mg, 0.18 mmol, 14%. LCMS m/z 349.0 [M+H+]. 1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.40 (s, 1H), 8.24 (br s, 1H), 7.98 (br d, J=7.5 Hz, 1H), 7.82 (br d, J=7.3 Hz, 1H), 7.63-7.70 (m, 2H), 3.39-3.45 (m, 4H), 3.13-3.20 (m, 4H).

後処理

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 30% to 50% B)

出典と根拠

ORDレコード
ord-39a8e98ef65f4abab14702b2ab48e2fa
出典データセット
uspto-grants-2015_10
特許番号
US09156845B2

反応ノート

読み込み中…