N,N-Dimethylglycine → 6-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

関与物質

役割	名称	HCID	仕込み量
反応物	N,N-Dimethylglycine	HCID 673	—
反応物	2-Isopropylphenol	HCID 6943	—
反応物	Cesium carbonate	HCID 10796	—
反応物	1,4-Dioxane	HCID 31275	—
反応物	3-(3-((tert-butyldimethylsilyl)oxy)propyl)-5-((4-chlorophenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 131737093	—
触媒	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
生成物	6-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 118875499	55%

反応手順

To a mixture of 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 400 mg, 1 mmol), CuI (24 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol) and 2-(dimethylamino)acetic acid (51 mg, 0.5 mmol) in dioxane (6 mL) was added 2-isopropylphenol (204 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 1.5 h then cooled to RT and filtered. The filtrate was diluted with EA (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (1:1) to give 6-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (250 mg, 55% yield) as a solid. LCMS: [MH+-THP] 370 and TR=0.918 min.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09440972B2
出典データセット	uspto-grants-2016_09
ORD ID	ord-2e0f8dbbaacd48aba9a0d9ac3d395af9
出典メモ	uspto-grants-2016_09