Chemical Properties
Off-White Solid
Uses
A metabolite of Gemcitabine (G305000) in human plasma.
Uses
A metabolite product of Gemcitabine
Definition
ChEBI: 2',2'-Difluorodeoxyuridine is a pyrimidine 2'-deoxyribonucleoside.
Synthesis
General procedure for the synthesis of 1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one hydrochloride from 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2,4(1H,3H)-dione As follows: 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one hydrochloride (5 g, 16.7 mmol, 1.0 eq.) was dissolved in 2N aqueous acetic acid (350 ml), sodium nitrite (16.7 g, 14.5 eq.) was added slowly and the reaction mixture The reaction mixture was allowed to stand at room temperature for 48 hours. Subsequently, the pH of the reaction mixture was adjusted to 6-7 with 2N aqueous sodium hydroxide and concentrated under reduced pressure. To the concentrated residue, a solvent mixture of methanol/ethyl acetate (1:5, 360 ml) was added and the insoluble salt was removed by filtration. This operation was repeated several times to remove the salt completely, and finally the filtrate was concentrated under reduced pressure to give 4.22 g of the target product 1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione as a light brown transparent oil in 95% yield.
References
[1] Patent: KR101794970, 2017, B1. Location in patent: Paragraph 0095-0097
[2] Patent: US2013/165400, 2013, A1
[3] Patent: WO2014/209979, 2014, A1
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 4, p. 1862 - 1878
[5] Patent: US2015/105341, 2015, A1
