تفاعل #69351

معادلة التفاعل

2-chloro-5-aminomethylpyridine

iPr2NEt

trifluoroacetic acid

2-((2R,6S,E)-5,12-dioxo-2-phenyl-1-oxa-4-azacyclododec-8-en-6-yl)acetic acid

EDC

HOBt

acetate

→

desired product

N-((6-chloropyridin-3-yl)methyl)-2-((2R,6S,E)-5,12-dioxo-2-phenyl-1-oxa-4-azacyclododec-8-en-6-yl)acetamide

المذيبات

CH2Cl2

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   أخرىconsumption of starting material
2. 2
   تركيزThe reaction mixture was concentrated
3. 3
   workup.ADDITIONwere subsequently added
4. 4
   workup.STIRRINGstirred for 16 h at which point LC-MS analysis
5. 5
   أخرىconsumption of starting material
6. 6
   workup.ADDITIONThe reaction mixture was diluted with saturated NH4Cl and EtOAc
7. 7
   أخرىthe layers separated
8. 8
   استخلاصThe aqueous was extracted 2× with EtOAc
9. 9
   غسيلthe combined organic extracts were washed with 1 N HCl and brine
10. 10
    تجفيفdried over Na2SO4
11. 11
    ترشيحfiltered
12. 12
    تركيزconcentrated
13. 13
    أخرىThe crude product was purified

الإجراء التجريبي

To a solution of tert-butyl 2R,6S,E)-5,12-dioxo-2-phenyl-1-oxa-4-azacyclododec-8-en-6-yl)acetate (200 mg, 0.516 mmol) in CH2Cl2 (397 mL) cooled in an ice/water bath was added trifluoroacetic acid (179 μL, 2.32 mmol) and the reaction mixture was stirred 1 h at which point LC-MS analysis indicated complete consumption of starting material. The reaction mixture was concentrated and a portion of the crude carboxylic acid was utilized immediately. To a solution of crude 2-((2R,6S,E)-5,12-dioxo-2-phenyl-1-oxa-4-azacyclododec-8-en-6-yl)acetic acid (86 mg, 0.260 mmol) in CH2Cl2 (3.2 mL) cooled in an ice/water bath was added EDC (74.6 mg, 0.389 mmol) and HOBt (52.6 mg, 0.389 mmol) and the resulting solution was stirred 30 min 2-chloro-5-aminomethylpyridine (40.7 mg, 0.285 mmol), iPr2NEt (139 μL, 0.779 mmol) and DMAP (3.2 mg, 0.026 mmol) were subsequently added and the reaction mixture was slowly warmed to rt and stirred for 16 h at which point LC-MS analysis indicated complete consumption of starting material. The reaction mixture was diluted with saturated NH4Cl and EtOAc and the layers separated. The aqueous was extracted 2× with EtOAc and the combined organic extracts were washed with 1 N HCl and brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified using silica gel chromatography (MeOH/CH2Cl2 gradient) to yield the desired product as a colorless oil. LRMS (M+H)+: 456.1.

المصدر