1-Butanol → HCID 67201776, compound

Participants

Reaction Steps

Compound C5 (1.59 g, 3.06 mmol) was dissolved in ˜6:1 EtOH:H2O (46 mL), Fe dust (885 mg) was added, and the resulting suspension brought to reflux. Two drops of c.HCl were added, and refluxing was continued for 1 h. (until TLC with the top phase of 5:4:1 mixture of n-BuOH:H2O:CH3CO2H showed complete consumption of starting material). The reaction mixture was diluted with EtOH (100 mL) and brought to reflux. The hot reaction mixture was filtered through a pad of Celite, and the top layer of the Celite pad was boiled with more EtOH and filtered (this procedure was repeated three times to ensure complete extraction of product from iron residues). The combined EtOH extracts were evaporated to dryness, and the residue was extracted with hot water, and filtered through a pad of Celite. The filtrate was concentrated to a smaller volume, and then stirred in pre-washed ion-exchange resin (55g). The resulting slurry was loaded onto a column packed with pre-washed ion-exchange resin and eluted with water. Fractions containing product were combined and evaporated to dryness, and the residue was azeotroped several times with EtOH. The residue was dissolved in a small volume of MeOH, methanolic HCl (1.25 M ,1 mL) was added, and the solution stirred for 10 min. The solution was diluted with EtOAc, and the resulting precipitate filtered and then crystallized from MeOH/EtOAc to give C6 (873 mg, 80%); mp (MeOH/EtOAc)>300° C.; 1H NMR [(CD3)2SO] δ10.77 (br s, 1 H, NH), 9.95 (s, 1 H, NH), 8.41 (br d, J=5.5 Hz, 2 H, Py H-2,6), 7.87-7.84 (m, 2 H, H-2,4), 7.61 (t, J=7.8 Hz, 1 H, H-5), 7.49 (br d, J=7.8 Hz, 1 H, H-6), 7.37 (d, J=8.7 Hz, 2 H, H-2′,6′), 7.21 (br d, J=4.6 Hz, 2 H py H-3,5), 6.55 (d, J=8.8 Hz, 2 H, H-3′,5′), 4.93 (s, 2 H, NH2), 3.97 (s, 3 H, N+CH3).

Provenance & Evidence