208993-54-8 (free base)
- Example 108
- 3-[4-((3aR,9bR)-cis -9-Methoxy-1,2,3,3a,4,9b-hexahydro--benzopyrano[3,4-c]pyrrol-2-yl)butyl]-8-(4-hydroxyphenyl)-pyrazino[2',3':4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione
- The product of Example 16 (0.07 g,0.105 mmol) and 4-(methoxymethyloxy) phenyl boronic acid (0.02 g, 0.11 mmol) prepared by the procedure described in Tetr.Lett., 31, 27, (1990) were treated as described in Example 106 to yield 0.029g(45%) of MOM-protected product. To the solution of this product (0.11g, 0.17 mmol) in CH3OH/THF was added 2N HCl (0.2ml) and the reaction mixture was refluxed for 1 hour. The reaction was evaporated and partitioned in NaHCO3 sol. and CH2Cl2/CH3OH to yield 0.005 g (51%) of the title compound.
- 1H NMR (500 MHz, CDCl3) d 1.81 (m, 2H), 1.98 (m, 2H), 2.25 (m, 1H), 2.65 (m, 1H), 2.88 (m, 1H), 3.08 (m, 2H), 3.22(m, 2H), 3.65 (m, 1H), 3.73 (m, 1H), 3.82 (s, 3H), 3.9 (m, 1H), 4.25 (m, 1H), 4.42 (m, 1H), 6.52 (m, 2H), 7.38 (m, 2H),7.49(m, 1H), 7.9 (t, 1H), 8.09 (d, 1H),9.12 (s, 1H);
- MS(ESI)m/e 572 (M+H)+.
- The product from Example 10 C (0.27 g, 1.0 mmol) and the product from Example 1E (0.20 g, 0.73 mmol) were treated as described in Example 1F to yield 0.29 g (77%) of the title compound: m.p. 220-222°;
- 1H NMR (300 MHz, CDCl3(free base)) δ 8.68 (s, 1H), 7.0 (t, 1H), 6.48 (d, 1H), 6.45 (d, 1H), 4.28 (m, 1H), 4.12 (m, 3H), 4.0 (m, 2H), 3.75 (s, 3H), 3.6 (m, 1H), 3.08 (m, 3H), 2.9 (m, 2H), 1.75 (m, 4H); MS (DCI/NH3) m/e 514(M+H)+;
- Analysis calc'd for C24H24ClN5O4S·HCl·0.75H2O: C, 51.11; H, 4.74; N, 12.42; found: C, 51.09; H, 4.75; N, 12.43.
In an alternative synthesis, phenylacetaldehyde (XVIII) was condensed with pyrrolidine (XIX) to give enamine (XX). Nitrosation of malononitrile (XXI), followed by treatment with tosyl chloride, produced the O-tosyl oxime (XXII). This was condensed with enamine (XX), and to the intermediate adduct (XXIII) was added thiophenol producing the phenylthiopyrazine (XXIV). Subsequent oxidation of the sulfide group of (XXIV) to sulfone (XXV), followed by condensation with methyl thioglycolate, gave the desired thienopyrazine (XIII).
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