Potassium Phosphate, Tribasic → 5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)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	Potassium Phosphate, Tribasic	HCID 62657	—
反応物	2-Isopropylbenzeneboronic acid	HCID 2773477	—
反応物	6-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 118875516	—
触媒	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
溶媒	1,4-Dioxane	HCID 31275	—
生成物	5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 118875549	42.8%

反応条件

温度	100 °C

反応手順

To a solution of 6-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (65 mg, 0.134 mmol) in dioxane (1 mL) was added (2-isopropylphenyl)boronic acid (88 mg, 0.536 mmol), Pd(dppf)Cl2 (10 mg) and aq. 2N K3PO4 (0.2 mL). The mixture was heated at 100° C. for 5 h, cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was purified by chromatography eluted with PE/EA (10:1 to 6:1) to give 5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 42.7% yield) as a solid. LCMS: [M+-THP-OH] 423 and TR=2.047 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-6c9ea7b0b6de4f8ba4875b9f73bcab13
出典メモ	uspto-grants-2016_09