تفاعل #332063

معادلة التفاعل

triethylamine

N,N-dimethylacrylamide

tri-ortho-tolylphosphine

7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

→

(2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide

المردود 63.8%

المذيبات

N,N-dimethylformamide

N,N-dimethylformamide

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىA thick walled glass vessel, equipped with a stir bar
2. 2
   workup.ADDITIONTo the solution was added in succession
3. 3
   أخرىThe reaction mixture was purged with nitrogen
4. 4
   أخرىThe vessel was sealed
5. 5
   درجة الحرارةThe reaction was cooled to ambient temperature
6. 6
   تركيزconcentrated to dryness under reduced pressure
7. 7
   workup.DISSOLUTIONThe resulting solid was dissolved in dichloromethane (100 mL)
8. 8
   غسيلwashed with saturated aqueous potassium carbonate (50 mL)
9. 9
   أخرىThe fractions were separated
10. 10
    تركيزthe organic fraction was concentrated to dryness
11. 11
    أخرىThe resulting off-white solid was purified by chromatography
12. 12
    أخرىA final recrystallization from acetonitrile

الإجراء التجريبي

A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.58 g, 1.5 mmol) in N,N-dimethylformamide (10 mL). To the solution was added in succession, a solution of palladium acetate (37 mg, 0.15 mmol) and tri-ortho-tolylphosphine (91 mg, 0.3 mmol) in N,N-dimethylformamide (5 mL), triethylamine (3.0 eq. 0.6 mL), and a solution of N,N-dimethylacrylamide (178 mg, 1.8 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (100 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness. The resulting off-white solid was purified by chromatography using a HORIZON HPFC system, (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 390 mg of (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide as an off-white crystalline solid, mp>260° C.

المصدر