Hydrochloric Acid → 2-(chloromethyl)-3H,4H-thieno[3,2-d]pyrimidin-4-one

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Chloroacetonitrile	HCID 7856	—
Reactant	Methyl 3-amino-2-thiophenecarboxylate	HCID 89652	—
Reactant	2-{4-[2-(2-cyclopentyl-4,6-dioxotetrahydro-2H-pyran-2-yl)ethyl]-2-fluorophenyl)-2-methylpropanenitrile	HCID 58762423	—
Reactant	{4-[2-(2-Cyclopentyl-4,6-dioxo-5-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile	HCID 68865868	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-(chloromethyl)-3H,4H-thieno[3,2-d]pyrimidin-4-one	HCID 135416191	85.4%

Reaction Steps

This compound was prepared by a modification of a method reported for related fused pyrimidine-4(3H)-ones: (1) Shishoo, C. J.; Devani, M. B.; Pathak, U.S.; Ananthan, S.; Bhadti, V. S.; Ullas, G. V.; Jain, K. S.; Rathod, I. S.; Talati, D. S.; Doshi, N. H. J. Heterocyclic Chem. 1984, 21, 375, and (2) Gerecke, M.; Kyburz, E.; Borer, R.; Gassner, W. Heterocycles 1994, 39, 693). An oven-dried 1-L round bottomed flask was charged with chloroacetonitrile (21.86 g, 0.29 mol, 1.3 equiv), methyl 3-aminothiophene-2-carboxylate (35 g, 0.223 mol), and 4 M HCl in 1,4-dioxane (350 mL). The reaction mixture was stirred at room temperature for 1 d. The mixture was evaporated to dryness. The residue was dissolved in water (600 mL) and treated with aqueous 10% sodium bicarbonate to a pH of 8. The resulting slurry was filtered, and the cake washed with water and dried, affording 38.2 g (85%) of the title product.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07148226B2
Source dataset	uspto-grants-2006_12
ORD ID	ord-a3288d5f2cce4c8c85de4727235fcaa7
Source note	uspto-grants-2006_12