Reaction #40509

Reaction equation

4-(2-amino-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide

2-methyl-nicotinic acid

EDCI

→

6,6-dimethyl-4-{2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide

Yield 80.5%

Solvents

water

pyridine

water

Conditions

Workup

1. 1
   workup.ADDITIONThe mixture was poured into a separatory funnel
2. 2
   ExtractionThe mixture was extracted with EtOAc (2×20 mL)
3. 3
   Washthe combined organic layers were washed with brine
4. 4
   DryingThe organic layer was dried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   Otherto yield a yellow-brown oil which
8. 8
   Otherwas purified via column chromatography
9. 9
   workup.DISSOLUTIONThe resulting yellow solid was dissolved in methanol (2 mL)
10. 10
    workup.ADDITIONHCl in Et2O (2M, 2 mL) was added
11. 11
    workup.STIRRINGThe mixture was stirred for 5 minutes
12. 12
    Concentrationconcentrated

Procedure

To a solution of 4-(2-amino-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (100 mg, 0.233 mmol) in pyridine (4 mL) was added 2-methyl-nicotinic acid (38.4 mg, 0.280 mmol) and EDCI (71.5 mg, 0.373 mmol). The solution was stirred overnight at room temperature, then diluted with water (5 mL). The mixture was poured into a separatory funnel and diluted further with water (20 mL). The mixture was extracted with EtOAc (2×20 mL), then the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield a yellow-brown oil which was purified via column chromatography. The resulting yellow solid was dissolved in methanol (2 mL) and HCl in Et2O (2M, 2 mL) was added. The mixture was stirred for 5 minutes, then concentrated to yield 103 mg of 6,6-dimethyl-4-{2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (71% yield).

Source