반응 #165855

반응 방정식

tert-butyl N-[[4-[5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]-3-chloro-phenyl]methyl]-N-methyl-carbamate

1,5-diphenylpenta-1,4-dien-3-one

1,5-diphenylpenta-1,4-dien-3-one

di-tert-butyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane

potassium hydroxide

TFA

ditert-butyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane

potassium hydroxide

→

product

수율 18.0%

2-[5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]-5-(methylaminomethyl)phenol

수율 18.0%

용매

dioxane

반응 조건

후처리

1. 1
   온도the resulting mixture heated for a further 2 h at 100° C
2. 2
   기타The reaction mixture was evaporated to dryness
3. 3
   기타the residue purified by column chromatography on silica eluting with 20% EtOAc/ petroleum ether
4. 4
   농축concentrated in vacuo
5. 5
   workup.DISSOLUTIONThis mixture was dissolved in DCM (10 mL)
6. 6
   농축concentrated in vacuo to an oil
7. 7
   기타This was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]
8. 8
   기타The product fractions were collected

실험 절차

To a solution of tert-butyl N-[[4-[5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]-3-chloro-phenyl]methyl]-N-methyl-carbamate (130 mg, 0.2170 mmol) in dioxane (3 mL) was added of 1,5-diphenylpenta-1,4-dien-3-one; palladium (6.239 mg, 0.01085 mmol), di-tert-butyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane (13.82 mg, 0.03255 mmol) and potassium hydroxide (434.0 μL of 1 M, 0.4340 mmol). The resulting mixture was heated to 100° C. for 2 h. Additional 1,5-diphenylpenta-1,4-dien-3-one; palladium (6.239 mg, 0.01085 mmol), ditert-butyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane (13.82 mg, 0.03255 mmol) and potassium hydroxide (434.0 μL of 1 M, 0.4340 mmol) were added and the resulting mixture heated for a further 2 h at 100° C. The reaction mixture was evaporated to dryness and the residue purified by column chromatography on silica eluting with 20% EtOAc/ petroleum ether. Product fractions were combined and concentrated in vacuo. This mixture was dissolved in DCM (10 mL) and TFA (247.4 mg, 167.2 μL, 2.170 mmol) added. The resulting mixture was stirred at room temperature for 1 h and then concentrated in vacuo to an oil. This was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3 CN) over 16 minutes at 25 mL/min]. The product fractions were collected and lypholised to give the product as a yellow solid (24.0 mg, 18% yield); 1H NMR (400.0 MHz, DMSO) d 1.31 (m, 6H), 2.80 (s, 3H), 3.43 (m, 1H), 4.27 (s, 2H), 7.23 (m, 1H), 7.30 (m, 1H), 8.04 (m, 2H), 8.19 (m, 1H), 8.41 (m, 2H) and 8.95 (s, 1H) ppm; MS (ES+) 481.2

출처