Sodium Carbonate → 5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)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	Sodium Carbonate	HCID 10340	—
反応物	3-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)	HCID 2734385	—
反応物	6-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 118875526	—
触媒	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
溶媒	Ethanol	HCID 702	—
溶媒	Toluene	HCID 1140	—
生成物	5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione	HCID 118875555	35.2%

反応条件

温度	100 °C

反応手順

To a solution of 6-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (75 mg, 0.138 mmol) in toluene (4 mL) and EtOH 1.3 mL) was added 3-(trifluoromethoxy)phenylboronic acid (43 mg, 0.208 mmol), Pd(dppf)Cl2 (10.7 mg) and aq. Na2CO3 (1M, 0.57 mL). The reaction was heated at 100° C. for 18 h, cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was purified by Prep TLC eluted with PE/EA (4:1) to give 5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 35.2% yield) as a solid. LCMS: MH+ 621 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-9202c7065b8b4ec9a3617819e1ac2623
出典メモ	uspto-grants-2016_09