Triethylamine → 5-Chloro-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic Acid [4-(3-dimethylamino-pyrrolidin-1-yl)phenyl]amide

[1-(4-Aminophenyl)pyrrolidin-3-yl]dimethylamine (32 mg) and carbonyldiimidazole (27.1 mg) were dissolved in acetonitrile (1.5 ml), and the mixture was stirred for 3 hours. Triethylamine (63.4 μl) was added to a solution of 5-chloro-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridine (40.7 mg) in THF (1 ml) and chloroform (0.5 ml). After 15 minutes, the mixture was added dropwise to the first solution and stirred overnight. The mixture was concentrated and the residue was partitioned between dichloromethane and water. The organic phase was dried over sodium sulfate, filtered and concentrated. Contamination by the primary and/or secondary amine was removed by dissolving the residue in dichloromethane (1.5 ml) and adding the solution to a stirred suspension of polymer-bound p-toluenesulfonyl chloride (0.5 g) in dichloromethane (6 ml) and triethylamine (128 μl). After 3 hours, the resin was filtered off and washed several times with dichloromethane. The combined organic phases were concentrated. The residue was purified by chromatography (silica gel, mobile phase: ethyl acetate/dichloromethane (5%), ammonia (7N in methanol, 2%), later ethyl acetate/dichloromethane (5%), ammonia (7N in methanol, 3%). This resulted in the product with the molecular weight of 425.97 (C23H28ClN5O); MS (ESI): 426 (M+H+).

1. waitAfter 15 minutes
2. additionthe mixture was added dropwise to the first solution
3. stirringstirred overnight
4. concentrationThe mixture was concentrated
5. customthe residue was partitioned between dichloromethane and water
6. dry with materialThe organic phase was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customContamination by the primary and/or secondary amine was removed
10. dissolutionby dissolving the residue in dichloromethane (1.5 ml)
11. additionadding the solution
12. additionto a stirred suspension of polymer-bound p-toluenesulfonyl chloride (0.5 g) in dichloromethane (6 ml) and triethylamine (128 μl)
13. waitAfter 3 hours
14. filtrationthe resin was filtered off
15. washwashed several times with dichloromethane
16. concentrationThe combined organic phases were concentrated
17. customThe residue was purified by chromatography (silica gel, mobile phase
18. customThis resulted in the product with the molecular weight of 425.97 (C23H28ClN5O)

ORD record

ord-10df67e345344ad6bb178ef340ce7f25

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07223788B2