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

참여 물질

역할	이름	HCID	투입량
반응물	2,6-Lutidine	HCID 7937	—
반응물	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
반응물	(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid	HCID 10017620	—
반응물	tert-butyl (2R,5S)-2-[2-(2-aminopyridin-3-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate	HCID 86726313	—
용매	Dimethylformamide	HCID 6228	—
용매	Ethyl Acetate	HCID 8857	—
용매	Sodium Bicarbonate	HCID 516892	—
생성물	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	—

반응 단계

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.

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US09315475B2
출처 데이터셋	uspto-grants-2016_04
ORD ID	ord-b2b957dacb19467d8520ec3ed9080c93
출처 메모	uspto-grants-2016_04