Реакция #2146777

Уравнение реакции

N,N-diethyl-2-hydroxy-benzamide

N,N′,N′-trimethylethane-1,2-diamine

(S)-2-(1-(4-bromophenyl)ethylamino)-9-cyclopentyl-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

N,N-diethyl-2-hydroxy-benzamide

K3PO4

N,N′,N′-trimethylethane-1,2-diamine

→

title compound

Выход 17.9%

(S)-9-cyclopentyl-2-(1-(4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)ethylamino)-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

Выход 17.9%

Растворители

DMF

ethyl acetate

water

ammonium hydroxide

Условия реакции

Обработка

1. 1
   ДругоеInto an oven dried Schlenk tube
2. 2
   Другоеdried under Argon
3. 3
   ДругоеThe tube was evacuated
4. 4
   workup.ADDITIONwas added
5. 5
   workup.ADDITIONthe tube was re-charged with argon
6. 6
   Температураheated to 90° C. overnight
7. 7
   ТемператураThe reaction mixture was then cooled to the ambient temperature
8. 8
   ЭкстракцияThe aqueous layer was extracted with ethyl acetate (four times, 5 mL each)
9. 9
   Сушкаdried with MgSO4
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated in vacuo
12. 12
    ДругоеThe crude product was purified by mass

Методика

Into an oven dried Schlenk tube dried under Argon was added (S)-2-(1-(4-bromophenyl)ethylamino)-9-cyclopentyl-5,7,7-trimethyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (100 mg, 0.2096 mmol), CuI (1.996 mg, 0.01048 mmol), N,N-diethyl-2-hydroxy-benzamide (8.101 mg, 0.04192 mmol) and K3PO4 (88.98 mg, 0.4192 mmol). The tube was evacuated and re-filled with Argon (three times), and N,N′,N′-trimethylethane-1,2-diamine (32.12 mg, 40.87 μL, 0.3144 mmol) in DMF (1 mL) was added and the reaction mixture was heated to 90° C. for 96 h. Additional CuI (1.996 mg, 0.01048 mmol), N,N-diethyl-2-hydroxy-benzamide (8.101 mg, 0.04192 mmol) and N,N′,N′-trimethylethane-1,2-diamine (214.2 mg, 272.5 μL, 2.096 mmol) were added to the tube and the tube was re-charged with argon and heated to 90° C. overnight. The reaction mixture was then cooled to the ambient temperature and diluted with ethyl acetate (5 mL), water (5 mL) and ammonium hydroxide (0.2 mL). The aqueous layer was extracted with ethyl acetate (four times, 5 mL each), dried with MgSO4, filtered and concentrated in vacuo. The crude product was purified by mass directed HPLC and product fractions combined and passed through a bicarbonate cartridge and lyophilized to give the title compound as a white solid (18.5 mg, 17% yield).

Источник