Sodium Azide → 1-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-ol

Participants

Reaction Conditions

Reaction Steps

To a microwave vial was added 5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (250 mg, 0.493 mmol), sodium azide (32.0 mg, 0.493 mmol), zinc bromide (111 mg, 0.493 mmol) and DMF (2463 μl). The tube was sealed and heated to 125° C. for 16 h. The reaction was cooled to rt and filtered, then purified by reverse phase HPLC using a C18 column with a solvent system containing MeCN and H2O modified with 0.1% TFA. Product containing fractions were lyophilyzed to give 1-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-ol (35 mg, 13%) as a white powder. MS ESI calcd for C26H21F3N8OS [M+H]+ 551, found 551. 1H NMR (600 MHz, dmso) δ 10.17 (s, 1H), 8.63 (s, 1H), 8.46 (d, J=4.8, 1H), 8.22 (s, 1H), 7.81 (s, 1H), 7.75 (d, J=7.8, 1H), 7.41 (d, J=8.1, 1H), 7.34 (s, 1H), 7.18 (d, J=4.0, 1H), 7.07 (s, 1H), 6.62 (s, 1H), 2.90 (d, J=4.3, 2H), 2.42-2.33 (m, 1H), 2.28 (s, 3H), 2.19-2.07 (m, 1H), 2.07-1.90 (m, 2H) ppm.

Provenance & Evidence