ETHYL 7-AMINOTHIENO[2,3-B]PYRAZINE-6-CARBOXYLATE

Step 7: synthesis of Ethyl 7-aminothieno[2, 3-b]pyrazine-6-carboxylate (7)A mixture of 3-chloropyrazine-2-carbonitrile (17.9 g, 128 mmol), sodium carbonate (17.7 g, 167 mmol) and ethyl-2-mercaptoacetate (18.4 mL, 167 mmol) in ethanol (120 mL) was heated to reflux for 4.5h. Quenched with water (1.5 L) and stirred for 30 min. The resulting precipitate was collected and washed with water. The residue was dissolved in diethyl ether and a black precipitate was filtrated off. Ether was evaporated to give pure compound ethyl 7-aminothieno[2, 3-b]pyrazine-6-carboxylate 7 (19.6 g, 68.5 percent). 1H-NMR (400 MHz, CDC1Step 7: Step 8: synthesis of 7-aminothieno[2, 3-b]pyrazine-6-carboxylic acid (8)A solution of Step 8: synthesis of 7-aminothieno[2, 3-b]pyrazine-6-carboxylic acid (8) A solution of 3-[4-((3aR, 9bS)-trans-9-Methoxy-1, 2, 3, 3a, 4, 9b-hexahydro-[1]-benzopyrano[3, 4-c]pyrrol-2-yl)butyl]-pyrazino'2', 3':4, 5thieno[3, 2-d]pyrimidine-2, 4(1H, 3H)-dione dihydrochloride Ethyl 7-amino-thieno[2, 3-b]pyrazine-6-carboxylate (0.32 g, 1.35 mmol) prepared by the method of Schneller and Clough, J. Het. Chem., 12: 513 (1975) and the product from Example 4A (0.31 g, 1.13 mmol) were treated as described in Example 1F to yield 0.28 g of the title compound as its free base. The product was converted to its HCl salt and recrystallized from ethanol/ether to yield the title compound: m.p. >250; 1 H NMR (300 MHz, DMSO-d6 (free base)) delta 8.98 (d, 1H), 8.89 (d, 1H), 7.11 (t, 1H), 6.52 (d, 1H), 6.45 (d, 1H), 4.5 (dd, 1H), 4.2 (m, 1H), 4.1 (m, 1H), 3.92 (m, 2H), 3.73 (s, 3H), 3.0 (m, 1H), 2.6 (m, 5H), 2.3 (m, 1H), 1.8 (m, 4H); MS (DCI/NH3) m/e 480(M+H)+; Analysis calc'd for C24 H25 N5 O4 S.2HCl.0.5H2 O: C, 51.34; H, 5.03; N, 12.47; found: C, 51.34; H, 4.95; N, 12.32.3-[4-((3aR, 9bS)-trans-9-Methoxy-1, 2, 3, 3a, 4, 9b-hexahydro-[1]-benzopyrano[3, 4-c]pyrrol-2-yl)butyl]-pyrazino]2', 3':4, 5]thieno[3, 2-d]pyrimidine-2, 4(1H, 3H)-dione dihydrochloride Ethyl 7-amino-thieno[2, 3-b]pyrazine-6-carboxylate (0.32 g, 1.35 mmol) prepared by the method of Schneller and Clough, J. Het. Chem., 12: 513 (1975) and the product from Example 4A (0.31 g, 1.13 mmol) were treated as described in Example 1F to yield 0.28 g of the title compound as its free base. The product was converted to its HCl salt and recrystallized from ethanol/ether to yield the title compound: m.p.>250; 1 H NMR (300 MHz, DMSO-d6 (free base)) delta 8.98 (d, 1H), 8.89 (d, 1H), 7.11 (t, 1H), 6.52 (d, 1H), 6.45 (d, 1H), 4, 5 (dd, 1H), 4.2 (m, 1H), 4.1 (m, 1H), 3.92 (m, 2H), 3.73 (s, 3H), 3.0 (m, 1H), 2.6 (m, 5H), 2, 3 (m, 1H), 1.8 (m, 4H); MS (DCI/NH3) m/e 480(M+H)+; Analysis calc'd for C24 H25 N5 O4 S.2HCl.0.5H2 O: C, 51.34; H, 5.03; N, 12.47; found: C, 51.34; H, 4, 95; N, 12, 32.Example 14B Ethyl 7-aminothieno[2, 3-b]pyrazine-6-carboxylate, 1-oxide A solution of Example 14A (2.90 g, 18.64 mmol) in DMF (100 mL) was treated with ethyl thioglycolate (2.24 g, 18.64 mmol), cooled to 0 C., treated with solid sodium ethoxide (2.54 g, 37.29 mmol) warmed to room temperature, stirred for 13 hours and partitioned between ethyl acetate and brine. The layers were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried (MgSO4) and concentrated to a yellow solid which was purified by column chromatography on silica gel with 2:1 then 1:1 hexanes/ethyl acetate to provide 3.50 g of the title compound as a yellow solid. MS (DCI/NH3) m/e 240 (M+H)+ and 257 (M+NH4)+.

Molecular Weight:223.25
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:3
Exact Mass:223.04154771
Monoisotopic Mass:223.04154771
Topological Polar Surface Area:106
Heavy Atom Count:15
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes