Dimethylamine → (6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester

HRID 402890ノート

反応式

HRID 402890 の反応式
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([CH:15]=O)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2].[CH3:18][NH:19][CH3:20].C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C1COCC1.CO.C(O)(=O)C.O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([CH2:15][N:19]([CH3:20])[CH3:18])[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2]

参加物

9

反応物 4

HCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 59192016Ethyl 2-(6-formylimidazo[1,2-a]pyridin-3-yl)acetate

生成物 1

HCID 59192025(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester収率 29%

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

(6-Formyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester (770 mg, 3.15 mmol) is dissolved in THF (10 ml) and treated with an excess of dimethylamine. The reaction mixture is stirred for 16 hours at room temperature in a stainless steel autoclave. A solution of sodium cyanoborohydride (229 mg, 3.46 mmol, 1.1 equiv) in MeOH (1.0 ml) and glacial acetic acid (1.1 ml) are added, and the solution is stirred for 1 hour at 60° C. The reaction mixture is diluted with water and adjusted to pH 8-9 by the addition of concentrated aqueous NaHCO3 solution. Extraction with EtOAc, washing with brine, drying over Na2SO4 and removal of solvent affords the crude reaction product. Purification via flash chromatography (EtOAc/cyclohexane 4:1, +0.2% NEt3) yields the title compound (242 mg, 29%). 1H NMR (400 MHz, CDCl3): δ=7.76-7.74 (m, 1H), 7.35 (dd, J=9.3/1.0 Hz, 1H), 7.31 (s, 1H), 6.99 (dd, J=9.1/1.7 Hz, 1H), 3.95 (q, J=7.1 Hz, 2H), 3.71 (s, 2H), 3.23 (s, 2H), 2.06 (s, 6H), 1.03 (t, J=7.1 Hz, 3H). MS (ES+): 262 (M+H)+.

後処理

  1. extractionExtraction with EtOAc
  2. washwashing with brine
  3. dry with materialdrying over Na2SO4 and removal of solvent
  4. customaffords the crude
  5. customreaction product
  6. customPurification via flash chromatography (EtOAc/cyclohexane 4:1, +0.2% NEt3)

出典と根拠

ORDレコード
ord-f4d66efd4fd447beac70955dfb45d069
出典データセット
uspto-grants-2014_06
特許番号
US08742132B2

反応ノート

読み込み中…