反应详情

In a round-bottomed flask, 2-(6-fluoro-3-hydroxymethyl-imidazo[1,5-a]pyridin-1-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 (82 mg, 0.138 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.43 ml, 5.6 mmol) was added. The reaction was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.56 ml, 8.3 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with dichloromethane. The resulting precipitate was filtered, washing with water and dichloromethane then dried under high vacuum to provide 46 mg (68%) of 2-(6-fluoro-3-hydroxymethyl-imidazo[1,5-a]pyridin-1-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 powder. MS: (M+H)+=463; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.30 (br. s, 1H), 9.12 (s, 1H), 8.79 (dd, J=9.6, 3.2 Hz, 1H), 8.55 (d, J=4.9 Hz, 1H), 8.44 (d, J=7.9 Hz, 1H), 8.40 (d, J=5.7 Hz, 1H), 7.07-7.17 (m, 1H), 5.61 (t, J=5.7 Hz, 1H), 4.94 (d, J=5.3 Hz, 2H), 4.50-4.81 (m, 3H), 4.20-4.32 (m, 1H), 4.14 (dt, J=10.3, 5.2 Hz, 1H), 3.81-3.93 (m, 1H), 1.40 (t, J=6.0 Hz, 3H).

1. concentrationthen concentrated
2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
3. stirringThe reaction mixture was stirred at room temperature for 1 h
4. customthen quenched with water
5. additiondiluted with dichloromethane
6. filtrationThe resulting precipitate was filtered
7. washwashing with water and dichloromethane
8. customthen dried under high vacuum