Diisopropylethylamine → N-(2-morpholinoethyl)-2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxamide

HRID 2096350

Reaktionsgleichung

Reaktionsgleichung von HRID 2096350
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[S:14][CH:15]=[C:16]([C:18]([OH:20])=O)[N:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:21][CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>S(Cl)(Cl)=O.CN(C=O)C>[O:27]1[CH2:28][CH2:29][N:24]([CH2:23][CH2:22][NH:21][C:18]([C:16]2[N:17]=[C:13]([C:10]3[CH:11]=[N:12][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:8][CH:9]=3)[S:14][CH:15]=2)=[O:20])[CH2:25][CH2:26]1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 4082852-MorpholinoethylamineHCID 592524752-(2-Phenylpyrimidin-5-yl)thiazole-4-carboxylic acid

Produkt 1

HCID 59252431N-(2-morpholinoethyl)-2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 24386Thionyl ChlorideLösungsmittel

Versuchsvorschrift

To a solution consisting of 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylic acid (Example 63, 172 mg, 0.61 mmol) in thionyl chloride (10 mL) was added one drop of dry DMF. The solution was heated at reflux for four hours and was subsequently allowed to reach room temperature and stirred for 18 hours. The thionyl chloride was evaporated away under reduced pressure and to the residue was added toluene (2×30 mL), which was evaporated and the residue subjected to high vacuum to remove residual thionyl chloride. The residue was dissolved in dichloromethane (10 mL) and 4-(2-aminoethyl)morpholine (51 mg, 0.051 mL, 0.40 mmol) was added followed by diisopropylethylamine (0.10 mL). The solution was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the residue partitioned between water and diethyl ether. The organics were dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel flash chromatography (100% dichloromethane to 9:1 v/v dichloromethane-methanol gradient) through a 40-g Silicycle® flash silica cartridge. The title compound was obtained as an off-white solid (63 mg, 61% yield); Rf 0.70 with 9:1 v/v dichloromethane-methanol; 1H-NMR (300 MHz; CDCl3) δ 9.30 (s, 2H), 8.51 (m, 2H), 8.20 (s, 1H), 7.88 (br t, 1H), 7.53 (m, 3H), 3.77 (t, 4H); 3.61 (dt, 2H), 2.64 (t, 2H), 2.54 (t, 4H); MS (ESI+) m/z 396 (M+1); H-PGDS FPBA IC50: 2.5 μM.

Aufarbeitung

  1. temperatureThe solution was heated
  2. temperatureat reflux for four hours
  3. customto reach room temperature
  4. customThe thionyl chloride was evaporated away under reduced pressure and to the residue
  5. additionwas added toluene (2×30 mL), which
  6. customwas evaporated
  7. customto remove residual thionyl chloride
  8. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  9. stirringThe solution was stirred at room temperature for 18 hours
  10. customThe solvent was removed under reduced pressure
  11. customthe residue partitioned between water and diethyl ether
  12. dry with materialThe organics were dried with anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by silica gel flash chromatography (100% dichloromethane to 9:1 v/v dichloromethane-methanol gradient) through a 40-g Silicycle® flash silica cartridge

Quellen und Nachweise

ORD-Eintrag
ord-cb5c80433d5c4c84aa5dfe51f97efc38
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08450326B2

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