Hydrochloric Acid → HCID 21100477, compound

Diisopropylamine (3.3 g) was dissolved in tetrahydrofuran (20 mL) and n-butyllithium (1.58M, hexane solution, 19 mL) was added dropwise under a nitrogen stream at −78° C. After the completion of the dropwise addition, a solution (20 mL) of N,N-diethyl-2,3-dimethylbenzamide (5.2 g) in tetrahydrofuran was added dropwise and the mixture was stirred for 1 hr. A solution (20 mL) of 3-(3,5-dimethyl-2-hydroxymethylpyrrolidin-1-yl)propionitrile (2.3 g) in tetrahydrofuran was added dropwise to the reaction mixture and the temperature of the reaction mixture was raised to room temperature. After the completion of the reaction, the reaction mixture was acidified by adding conc. hydrochloric acid. The reaction mixture was concentrated and washed with hexane. The aqueous layer was basified by adding potassium carbonate and extracted with chloroform. The organic layer was dried over magnesium sulfate. The solvent was concentrated and the obtained residue was purified by silica gel column chromatography. The fraction eluted with chloroform:methanol=30:1 was concentrated and the obtained residue was again purified by silica gel column chromatography (NH silica gel, Fuji Silysia Chemical). The fraction eluted with chloroform was concentrated and ether was added to the obtained residue. The precipitated crystals were collected by filtration to give 3-[2-(3,5-dimethyl-2-hydroxymethylpyrrolidin-1-yl)ethyl]-5-methyl-2H-isoquinolin-1-one (0.5 g).

1. additionAfter the completion of the dropwise addition
2. customAfter the completion of the reaction
3. concentrationThe reaction mixture was concentrated
4. washwashed with hexane
5. additionby adding potassium carbonate
6. extractionextracted with chloroform
7. dry with materialThe organic layer was dried over magnesium sulfate
8. concentrationThe solvent was concentrated
9. customthe obtained residue was purified by silica gel column chromatography
10. washThe fraction eluted with chloroform
11. concentrationmethanol=30:1 was concentrated
12. customthe obtained residue was again purified by silica gel column chromatography (NH silica gel, Fuji Silysia Chemical)
13. washThe fraction eluted with chloroform
14. concentrationwas concentrated
15. additionether was added to the obtained residue
16. filtrationThe precipitated crystals were collected by filtration

ORD record

ord-49e1f421039f49b8a87c2c689ec8ed41

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812178B2