Hydrochloric Acid → HCID 25177313, compound

Participants

Reaction Steps

An aqueous solution of 1N lithium hydroxide (0.263 ml) was added at 0° C. to a methanol/tetrahydrofuran solution (1:10 v/v, 2.5 ml) mixed with (S)-4-amino-19,21-dimethyl-10,17-dioxo-7-thia-3,5,11,16-tetraazatricyclo[16.3.1.12,6]tricosa-1(21),2,4,6(23),18(22),19-hexaene-12-carboxylic acid methyl ester (30 mg) obtained in Step 3 of Example 2-9. After stirring for 10 minutes, the mixture was warmed to room temperature and stirred for 1.5 hours. The pH of the reaction solution was adjusted to about 4 using 1N hydrochloric acid. The solution was extracted four times with ethyl acetate (20 ml). The organic layers were combined together, and dried over anhydrous sodium sulfate. After the inorganic salt was removed by filtration, the filtrate was concentrated under reduced pressure to give crude product (39 mg). An aliquot (20 mg) of the crude product was dissolved in N,N-dimethylformamide (1.0 ml), and then 2-3H-1,2,3-triazolo[4,5-b]pyridin-3-ol (7 mg, 0.053 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (20 mg, 0.052 mmol),2,4,6-trimethylpyridine (14 μl), and 2-aminoethanol (3 μl, 0.053 mol) were added thereto at 0° C. After stirring at 0° C. for 30 minutes, the mixture was warmed to room temperature and stirred for 30 minutes. The reaction solution was concentrated under reduced pressure. The resulting crude product was purified by high performance liquid chromatography (developing solvent: A, acetonitrile containing 0.05% trifluoroacetic acid; B, 0.05% aqueous trifluoroacetic acid solution; gradient condition: B, 1% (0 min)→1% (1 min)→30% (7 min)→95% (8 min)→95% (9 min)→1% (10 min); flow rate, 35 ml/min; column, Waters, SunFire PrepC18, 5 μm, 30×50 mm). A fraction containing the material of interest was neutralized with solid-supported tetraalkyl ammonium carbonate (Polymer Laboratories, PL-HCO3 MP-Resin) to yield (S)-4-amino-19,21-dimethyl-10,17-dioxo-7-thia-3,5,11,16-tetraazatricyclo[16.3.1.12,6]tricosa-1(21),2,4,6(23),18(22),19-hexaene-12-carboxylic acid (2-hydroxyethyl) amide (Compound 46) (7 mg) was obtained as a white solid material.

Provenance & Evidence