反応 #163552

反応方程式

4-fluoro-3-methyl-benzene-1,2-diamine

Na2S2O5

sodium metabisulfite

4-methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbaldehyde

triethylamine

HCl

→

title compound

[5-(5-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine

溶媒

DMF

反応条件

後処理

1. 1
   濃縮The resultant mixture was then concentrated
2. 2
   その他partitioned between dichloromethane (1 L) and 1 N NaOH (1 L)
3. 3
   その他After separation of the layers
4. 4
   抽出the aqueous layer was extracted a second time with dichloromethane (1 L)
5. 5
   洗浄The combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L)
6. 6
   抽出The organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L)
7. 7
   抽出The resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL)
8. 8
   濃縮the combined organics were concentrated

実験手順

To a 2 L Erlenmeyer flask were added 4-fluoro-3-methyl-benzene-1,2-diamine.HCl (46.32 g, 262.3 mmol), Na2S2O5 (64.82 g, 341.0 mmol), and 4-methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbaldehyde (72.5 g, 262.3 mmol) in DMF (725 mL). To the resultant mixture was then added triethylamine (36.6 mL, 262.3 mmol), and the reaction was warmed on a hot plate with stirring to 90° C. and held at this temperature for 2 hours. The resultant mixture was then concentrated to near dryness and partitioned between dichloromethane (1 L) and 1 N NaOH (1 L). After separation of the layers, the aqueous layer was extracted a second time with dichloromethane (1 L). The combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L). The organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L). The aqueous layer was then basified with 50% NaOH (80 mL) to pH 10.8. The resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL), and the combined organics were concentrated to yield the title compound.

出典