反应详情

In a round-bottomed flask, 5-(2-trimethylsilanyl-ethoxymethyl)-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-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 (112 mg, 0.19 mmol) was dissolved in dichloromethane (0.9 ml) and trifluoroacetic acid (0.6 ml, 7.5 mmol) was added. The yellow solution was stirred at room temperature for 2.5 h then concentrated. The residue was redissolved in dichloromethane (0.9 ml) and ethylenediamine (0.8 ml, 11.4 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 47 mg (51%) of 2-(1,5,5-Trimethyl-4,5,6,7-tetrahydro-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 white powder. MS: (M+H)+=461; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.61 (br. s., 1H), 8.94 (s, 1H), 8.27-8.41 (m, 2H), 4.43-4.80 (m, 3H), 3.94-4.24 (m, 2H), 3.80 (s, 3H), 3.72-3.91 (m, 1H), 2.89 (d, J=15.9 Hz, 1H), 2.59-2.71 (m, 3H), 1.59 (t, J=6.2 Hz, 2H), 1.40 (dd, J=6.8, 3.0 Hz, 3H), 1.00 (s, 6H).

1. concentrationthen concentrated
2. dissolutionThe residue was redissolved in dichloromethane (0.9 ml)
3. stirringThe reaction mixture was stirred at room temperature for 1 h
4. customthen quenched with water
5. additiondiluted with ethyl acetate
6. filtrationThe resulting suspension was filtered
7. washwashed with hot water and ethyl acetate
8. customdried under high vacuum