Réaction #165351

Équation de réaction

2-picolyl chloride

sodium hydroxide

2-picolyl chloride hydrochloride

4-(5-(2-amino-6-methoxymethyl-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol

sodium hydroxide

→

2-picolyl chloride

title compound

Rendement 52.0%

6-Methoxymethyl-3-(3-(4-(pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Rendement 52.0%

Solvants

Water

methanol

Conditions de réaction

Traitement

1. 1
   Concentrationwas concentrated under a reduced pressure
2. 2
   workup.ADDITIONN,N-dimethylformamide (1.5 mL) was added to the residue
3. 3
   Autrethus obtained at room temperature
4. 4
   workup.ADDITIONwas added to the reaction mixture at the same temperature
5. 5
   Extractionwas extracted with ethyl acetate
6. 6
   LavageThe organic layer was washed with water and saturated aqueous sodium chloride
7. 7
   Concentrationwas concentrated under a reduced pressure
8. 8
   AutreThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1)

Mode opératoire

To a methanol (1.5 mL) solution of 4-(5-(2-amino-6-methoxymethyl-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol (50 mg, 0.16 mmol) described in Manufacturing Example 166-1-1 was added a 1 N sodium hydroxide aqueous solution (160 μL, 0.16 mmol), which was concentrated under a reduced pressure. N,N-dimethylformamide (1.5 mL) was added to the residue thus obtained at room temperature, and 2-picolyl chloride (29 mg, 0.23 mmol; this 2-picolyl chloride was prepared by adding a 5 N sodium hydroxide aqueous solution to 2-picolyl chloride hydrochloride) was added to the reaction mixture at the same temperature. The reaction mixture was stirred for 100 minutes at the same temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1) to obtain the title compound (32 mg, 52%).

Source