Cesium carbonate → Methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate

https://huagongshe.com/ko/reaction/340508

참여 물질

역할	이름	HCID	투입량
반응물	Cesium carbonate	HCID 10796	—
반응물	4-Bromoisoquinoline	HCID 73743	—
반응물	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
반응물	Methyl2-amino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoronicotinate	HCID 86683887	—
촉매	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
용매	Water	HCID 962	—
용매	Ethyl Acetate	HCID 8857	—
용매	1,4-Dioxane	HCID 31275	—
생성물	Methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate	HCID 86683886	72.2%

반응 조건

온도	100 °C

반응 단계

4-bromoisoquinoline (65 mg), cesium carbonate (170 mg), Pd2(dba)3 (29 mg), and Xantphos (36 mg) were added to a 1,4-dioxane (2.1 ml) solution containing methyl 2-amino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoronicotinate (80 mg), followed by stirring at 100° C. for 3 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. Insoluble matter was removed by filtration, and the filter cake was washed with water and ethyl acetate. The organic layer was collected, washed with saturated saline, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 1:2), diisopropylether was added, solid matter was collected by filtration, and a light yellow solid of methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate (77 mg) was obtained.

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US08895585B2
출처 데이터셋	uspto-grants-2014_11
ORD ID	ord-4f5dfba8290e4dcb8ff5b6ab69298b73
출처 메모	uspto-grants-2014_11