Reacción #639411

Ecuación de reacción

water

DCM

(S)-4-((S)-2-Amino-propyl)-6,6-dimethyl-morpholine-3 carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide hydrochloride salt

methyl chloroformate

→

desired product

Rendimiento 77.0%

{(S)-2-[(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl]-carbamic acid methyl ester

Rendimiento 77.0%

Disolventes

pyridine

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónthe mixture was concentrated to dryness
2. 2
   OtroThe residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3
3. 3
   ExtracciónThe separated aqueous phase was extracted with 50 ml of EtOAc
4. 4
   LavadoThe combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml)
5. 5
   Secadodried over Na2SO4
6. 6
   Concentraciónconcentrated to dryness
7. 7
   OtroThe residue was purified on silica (5% MeOH/CH2Cl2)

Procedimiento

To a solution of (S)-4-((S)-2-Amino-propyl)-6,6-dimethyl-morpholine-3 carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide hydrochloride salt (3.45 g, 6.59 mmole) in 68 ml of dry pyridine, was added in three portions over 1.5 hr, a 3M DCM solution of methyl chloroformate (9.2 ml, 27.6 mmole, 4.2 eq). After 2 h, 10 ml of water were added and the mixture was concentrated to dryness. The residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3. The separated aqueous phase was extracted with 50 ml of EtOAc. The combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml), dried over Na2SO4 and concentrated to dryness. The residue was purified on silica (5% MeOH/CH2Cl2) to give 2.48 g (thick oil, 77% yield) of the desired product 1H-NMR (300 MHz, CDCl3): δ 1.15 (d, 3H), 1.28 (s, 3H), 1.42 (s, 3H), 2.33 (dd, 1H), 2.42 (d, 1H), 2.78 (dd, 1H), 2.86 (d, 1H), 3.32 (dd, 1H), 3.86 (s, 3H), 3.92 (t, 1H), 4.01 (dd, 1H), 4.18 (m, 1H), 4.78 (d, 1H), 7.95 (d, 1H), 7.97 (s, 1H), 8.29 (s, 1H), 8.50 (d, 1H), 8.98 (s, 1H), 9.88 (s, 1H), 10.94 (s, 1H). Retention Time (LC, method: ammonium acetate standard): 1.70 min. MS (M+H+): 474.1

Fuente