Diisopropylethylamine → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-chloropyridin-2-ylcarbamate

関与物質

役割	名称	HCID	仕込み量
反応物	Diisopropylethylamine	HCID 81531	—
反応物	P,P-Diphenylphosphinic azide	HCID 199401	—
反応物	5-Chloro-2-picolinic acid	HCID 2762872	—
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-chloropyridin-2-ylcarbamate	HCID 57947593	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 (480 mg, 1.07 mmol), 5-chloropicolinic acid (339 mg, 2.15 mmol), and DIEA (0.36 mL, 2.15 mmol) in toluene (10 mL) was added DPPA (0.46 mL, 2.15 mmol). The reaction mixture was heated to 100° C. for 2 h and concentrated to dryness. The residue was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(1,3-dioxoisoindolin-2-yl)pentyl 5-chloropyridin-2-ylcarbamate (280 mg, 80% pure). LRMS (M+H+) m/z 602.2.

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-d355a325016042d2938d4cc3a3350a86
出典メモ	uspto-grants-2014_06