反应详情

A solution of an acid 503 (334 mg, 1.22 mmol) in DMF (1.67 mL) was treated with HBTU (462 mg, 1.22 mmol) followed by DIEA (452 mg, 3.5 mmol) and stirred for 5 min. 3-Amino-1-methyl-5-methyloxycarbonylpyrrol hydrochloride (232 mg, 1.22 mmol) and DIEA (378 mg, 3 mmol) were added to the reaction mixture. The latter was stirred for 2 h, diluted with Et2O, the precipitate was removed, dissolved in CHCl3, washed with 3% HCl, H2O, aqueous NaHCO3, H2O again, dried (MgSO4) and purified by chromatography on alumina column (CHCl3/MeOH 80:1, 50:1). The product was triturated with Et2O/CHCl3 to obtain a yellow-red solid (200 mg, 40%); mp 122-123° C. (decomp.): MS (LSIMS, 3-NBA) 410 (M+), 237 (M+−173). 1H NMR (CDCl3) 8.08 (d, J=7.5 Hz, 1H), 7.86 (d, J=7.3 Hz, 1H), 7.68 (t, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.38 (d, J=1.8 Hz, 1H), 7.34 (s, 1H), 6.65 (d, J=2 Hz, 1H), 5.95 (s, 1H), 4.19 (t, J=5.53 Hz, 2H), 3.88 (s, 3H), 3.80 (s, 3H), 2.46 (t, J=6.6 Hz, 2H), 1.90-2.15 (m, 4H).

1. stirringThe latter was stirred for 2 h
2. customthe precipitate was removed
3. dissolutiondissolved in CHCl3
4. washwashed with 3% HCl, H2O, aqueous NaHCO3, H2O again
5. dry with materialdried (MgSO4)
6. custompurified by chromatography on alumina column (CHCl3/MeOH 80:1, 50:1)
7. customThe product was triturated with Et2O/CHCl3