2,3-Dihydropyrido[2,3-d][1,3]oxazol-2-one

Chemical Properties

Tan Solid

Uses

2,3-Dihydropyrido[2,3-d][1,3]oxazol-2-one is a benzoxazolone analogue that may be used to inhibit the nitric oxide synthases (NOS).

Definition

ChEBI: Oxazolo[4,5-b]pyridin-2(3H)-one is a lactone. It derives from a hydride of an oxazolo[4,5-b]pyridine.

Synthesis

N,N'-Carbonyldiimidazole (57.4 g, 354.2 mmol) was slowly added to a tetrahydrofuran (THF) solution (400 mL) of 2-amino-3-hydroxypyridine (26.0 g, 236.1 mmol, purchased from Aldrich) as described in Step 4-i of Scheme 4. The resulting reaction mixture was stirred at 70 °C for 14 hours. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The concentrated residue was dissolved in dichloromethane (DCM) (500 mL) and subsequently washed with 2N sodium hydroxide (NaOH) solution (3 x 100 mL). The aqueous phases were combined, cooled to 0 °C, and the pH was adjusted to 6 with 6 N hydrochloric acid (HCl).At this point, the product precipitated as a precipitate, which was collected through a sintered funnel and washed with cold water (100 mL). Finally, the product was dried under vacuum to afford 2,3-dihydropyrido[2,3-d][1,3]oxazol-2-one (compound 1011, 26.0 g, 81% yield). The product was characterized by the following data: electrospray mass spectrometry (ESMS) (M + H) + m/z 137; 1H NMR (DMSO-d6) δ 12.4 (br, 1H), 8.0 (d, 1H), 7.6 (d, 1H), 7.1 (dd, 1H).

References

[1] Patent: WO2007/67416, 2007, A2. Location in patent: Page/Page column 56; 91
[2] Patent: WO2010/96389, 2010, A1. Location in patent: Page/Page column 42; 44
[3] Patent: WO2010/135014, 2010, A1. Location in patent: Page/Page column 50-51
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8066 - 8096
[5] Patent: WO2009/23844, 2009, A2. Location in patent: Page/Page column 120