Thiazole → (R)-8-cyclopentyl-7-ethyl-5-methyl-2-(thiazol-2-yl)-7,8-dihydropteridin-6(5H)-one

Participants

Role	Name	HCID	Charge
Reactant	Thiazole	HCID 9256	—
Reactant	(R)-2-Chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one	HCID 24820413	—
Reactant	Butyllithium	HCID 178418339	—
Catalyst	Zincchloride	HCID 3007855	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Tetrahydrofuran	HCID 8028	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(R)-8-cyclopentyl-7-ethyl-5-methyl-2-(thiazol-2-yl)-7,8-dihydropteridin-6(5H)-one	HCID 58405880	—

Reaction Conditions

Temperature	-78 °C

Reaction Steps

To a solution of thiazole (5 eq) in dry THF, BuLi (5 eq) was added dropwise at −78° C. and this was stirred at −78° C. for 30 min. ZnCl2 (1M in ether, 5 eq) was added and stirred at 0° C. for 30 min, then Intermediate B (1 eq) and Pd(dppf)Cl2 (0.1 eq) were added. The reaction was heated to 70° C. for 16 h; then the mixture was diluted with EtOAc, washed with brine and concentrated. The residue was purified by silica gel flash chromatography to give the title compound. LCMS (0.05% TFA): 344.1 m/z (M+H)+; 1H-NMR (MeOD, 500 MHz): δ: 8.04 (bs, 1H), 7.99 (bs, 1H), 7.76 (bs, 1H), 4.41 (m, 2H), 3.42 (s, 3H), 2.16 (m, 2H), 2.09˜1.72 (m, 8H), 0.88 (t, 3H, J=7.5 Hz).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08541418B2
Source dataset	uspto-grants-2013_09
ORD ID	ord-d3cea99faf724492bd6cb6e3a501f84e
Source note	uspto-grants-2013_09