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

HRID 42316

反応式

HRID 42316 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 24386Thionyl Chloride溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-43cd944fae24486b9ed113053a1f71bc
出典データセット
uspto-grants-2013_09
特許番号
US08536185B2

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