反应详情

In a 10 mL pear-shaped flask, 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (130 mg, 0.20 mmol) was combined with CH2Cl2 (1 ml) to give a yellow solution. TFA (0.24 ml, 3.2 mmol) was added and the reaction was stirred at room temperature for 2 h. The crude reaction mixture was concentrated in vacuo and redissolved in CH2Cl2. Ethylenediamine (0.33 ml, 5.0 mmol) was added dropwise and the reaction was stirred at room temperature for 20 min. The crude reaction mixture was concentrated in vacuo. The residue was suspended in cold water and filtered, washing with water then dried on high vacuum to give 70 mg (64%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow solid. MS: (M+H)+=520; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.70 (d, J=7.0 Hz, 1H), 8.36-8.63 (m, 2H), 8.03 (s, 1H), 7.25 (d, J=6.6 Hz, 1H), 4.48-4.82 (m, 5H), 4.16-4.34 (m, 1H), 4.01-4.15 (m, 1H), 3.86 (d, J=5.1 Hz, 1H), 3.33 (br. s., 1H), 2.80 (t, J=6.1 Hz, 2H), 2.20 (s, 6H), 1.40 (t, J=6.4 Hz, 3H).

1. customto give a yellow solution
2. customThe crude reaction mixture
3. concentrationwas concentrated in vacuo
4. dissolutionredissolved in CH2Cl2
5. stirringthe reaction was stirred at room temperature for 20 min
6. customThe crude reaction mixture
7. concentrationwas concentrated in vacuo
8. filtrationfiltered
9. washwashing with water
10. customthen dried on high vacuum