Dimethylacetamide → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-(trifluoromethyl)pyridin-2-ylcarbamate

関与物質

役割	名称	HCID	仕込み量
反応物	Dimethylacetamide	HCID 31374	—
反応物	P,P-Diphenylphosphinic azide	HCID 199401	—
反応物	5-(trifluoromethyl)pyridine-2-carboxylic Acid	HCID 10910349	—
反応物	(S)-3-(2-chloro-3-fluorobenzyl)-1-(5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl)-1-methylurea	HCID 57947359	—
溶媒	Toluene	HCID 1140	—
生成物	(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-(trifluoromethyl)pyridin-2-ylcarbamate	HCID 57947787	80%

反応条件

温度	100 °C

反応手順

To a solution of (S)-3-(2-chloro-3-fluorobenzyl)-1-(5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl)-1-methylurea (200 mg, 0.45 mmol), 5-(trifluoromethyl)picolinic acid (256 mg, 1.35 mmol) and DMA (0.3 mL, 1.35 mmol) in toluene (5 mL) was added DPPA (0.27 mL, 1.35 mmol). The mixture was heated to 100° C. for 2 h, and concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-(trifluoromethyl)pyridin-2-ylcarbamate (150 mg, 80%). LRMS (M+Na+) m/z 658.2.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08759374B2
出典データセット	uspto-grants-2014_06
ORD ID	ord-d070e973eed5444886eba12bb16a4a03
出典メモ	uspto-grants-2014_06