The mixture was poured in cold water, the white solid was filtered, washed with water and recrystallized from absolute ethanol to afford 2a b as white solids. 2a. Yield 37%, mp 194 195uC. 1H NMR: d 1.44, three.90, three.98, four.38 4.48 and 4.50 four.58, five.19 5.22, 7.24 7.37, eight.06, 11.06. IR : 3300 3100, 1704. Anal. C, H, N, S. 2b. Yield 55%, mp 213 214uC. 1H NMR: d 1.42 1.74 and 1.94 2.27, three.76 three.97, 4.17 four.42, four.92 five.12, five.57, 7.03 7.28, 7.87, 12.19. IR : 3150 2850, 1703. Anal. C, H, N, S. General procedure for the synthesis of 6 four chloro 1 1H pyrazolopyrimidines. The Vilsmeier complex, previously prepared from POCl3 andanhydrousDMFwas added to a suspension in the suitable Rho-associated protein kinase compound 2a b in CHCl3. The mixture was refluxed for eight h. The remedy was washed with iced water, dried, filtered, and concentrated underneath reduced pressure. The crude oil was purified by column chromatography using diethyl ether because the eluant, to afford the pure goods 3a b as white solids. 3a. Yield 74%, mp 67 68uC. 1H NMR: d 1.45, 1.49, 4.00, four.74 4.82 and 4.88 four.97, five.45 5.55, 7.21 7.50, eight.00. Anal. C, H, N, S. 3b. Yield 63%, mp 70 71uC. 1H NMR: d 1.54 1.85 and 2.10 two.32, 3.93 4.07, four.67 4.80 and four.82 4.97, 5.38 five.50, 7.19 7.42, 7.94. Anal. C, H, N, S. Synthesis of 1 6 methyl 1,five dihydro 4H pyrazolopyrimidin 4 one particular.
To a resolution of 5 amino 1 1H pyrazole four carboxamide 6 in absolute ethanol, a option of sodium ethoxide ready from sodium and absolute ethanol and ethyl acetate JAK Inhibitors were added. The mixture was refluxed for 6 h, soon after cooling, ice water was added and the option was acidified with 3% acetic acid.
The precipitated solid was filtered, washed with water and recrystallized from absolute ethanol to afford compound 7 as a white solid, yield 60%, mp 253 254uC. 1H NMR: d 2.25, four.07 four.20 and four.27 4.42, 4.92 5.06, 5.52, 7.ten 7.30, 7.90, 11.91. IR : 3400 3150, 1660. Anal. C, H, N. Synthesis of four chloro six methyl 1H pyrazolopyrimidine. The Vilsmeier complicated, previously ready from POCl3 and anhydrous DMF was added to a suspension of 1 6 methyl 1,5 dihydro 4H pyrazolo pyrimidin four one 7 in CHCl3. The mixture was refluxed for 12 h. The remedy was washed with water, dried, filtered and concentrated below lowered pressure. The crude oil was purified by column chromatography, applying diethyl ether because the eluant, to afford eight as a yellow oil, which crystallized standing in a refrigerator by adding a 1:1 mixture of diethyl ether/petroleum ether as a white strong, yield 67%, mp 96 97uC. 1HNMR: d 2.69, 4.68 four.81 and four.90 5.04, five.39 five.51, 7.
16 7.41, 8.01. Anal. C, H, N. Basic process for the synthesis of compounds four, 5, 9, 10 Process A. To a solution from the proper 4 chloro derivative 3b and eight in absolute ethanol the appropriate aniline was added along with the mixture was refluxed for 4 h. Immediately after cooling, the white strong was filtered, washed with water and recrystallized from absolute ethanol. four. Yield 54%, mp 237 238uC. 1H NMR: d 1.41 1.70 and 2.02 two.23, 3.87 four.03, 4.62 4.73, 5.51 5.64, 7.03 7.ten, 7.20 7.44, 7.52 7.63 and eight.00 8.09, 8.23. IR : 2937. Anal. C, H, N, S. 9. Yield 58%, mp 269 270uC. 1H NMR: d 2.69, four.45 four.66 and 4.78 4.94, five.25 5.37, 7.00, 7.14 7.58, 12.60. IR : 2966. Anal. C, H, N. 10. Yield 55%, mp 245 246uC. 1H NMR: d two.69, 4.55 four.72 and four.80 four.98, five.27 five.39, six.99, 7.16 7.53. IR : 3100. Anal. C, H, N.