2,6-Lutidine → tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}pyridin-3-yl)ethyl]morpholine-4-carboxylate

関与物質

役割	名称	HCID	仕込み量
反応物	2,6-Lutidine	HCID 7937	—
反応物	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
反応物	(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid	HCID 10017620	—
反応物	tert-butyl (2R,5S)-2-[2-(2-aminopyridin-3-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate	HCID 86726313	—
溶媒	Dimethylformamide	HCID 6228	—
溶媒	Ethyl Acetate	HCID 8857	—
溶媒	Sodium Bicarbonate	HCID 516892	—
生成物	tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}pyridin-3-yl)ethyl]morpholine-4-carboxylate	HCID 86726314	—

反応手順

To N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (1.1 eq.) in DMF (0.15 M) at rt were added HATU (1.4 eq.) and 2,6-lutidine (3 eq.). The reaction mixture was stirred for 30 min and tert-butyl (2R,5S)-2-[2-(2-aminopyridin-3-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (1 eq) was added. The reaction mixture was stirred at 60° C. for 16 h and diluted with EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by automated SiO2 flash chromatography system using solvent gradient of 0% to 10% MeOH/CH2Cl2 to afford the desired compound. Alternatively, DMF could be replaced as solvent by pyridine to ease coupling involving less reactive amine.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09315475B2
出典データセット	uspto-grants-2016_04
ORD ID	ord-b2b957dacb19467d8520ec3ed9080c93
出典メモ	uspto-grants-2016_04