Diisopropylethylamine → tert-Butyl 2-methyl-1-((S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido) ethyl) pyrrolidin-2-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oate

関与物質

役割	名称	HCID	仕込み量
反応物	Diisopropylethylamine	HCID 81531	—
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	Methylamino-PEG3-t-butyl ester	HCID 53662991	—
反応物	HCID 66588141	HCID 66588141	—
溶媒	Dimethylformamide	HCID 6228	—
溶媒	Ethyl Acetate	HCID 8857	—
生成物	tert-Butyl 2-methyl-1-((S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido) ethyl) pyrrolidin-2-yl)-1-oxo-5,8,11-trioxa-2-azatetradecan-14-oate	HCID 86705970	37%

反応条件

温度	60 °C

反応手順

To a mixture of (S)-1-(2-(N-methyl-3-((4-(piperidin-1-yl)-2-(4-(((S)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzamido)ethyl)pyrrolidine-2-carboxylic acid (0.035 mmol, 25.7 mg), tert-butyl 5,8,11-trioxa-2-azatetradecan-14-oate 135c (0.042 mmol, 12.4 mg) and DIEA (0.212 mmol, 27 mg) in DMF (0.15 mL) was added HATU (0.042 mmol, 16 mg). The mixture was stirred at 60° C. for 1 h. The reaction mixture was diluted with ethyl acetate, washed with water (2×), brine (1×), dried and concentrated. 23% of the residue was purified by prep. HPLC to give a yellow solid (4 mg, 37%). MS (ES, m/z): 1002.36 [M+H]+.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09301951B2
出典データセット	uspto-grants-2016_04
ORD ID	ord-267635befdc74bbb9204841bac66725d
出典メモ	uspto-grants-2016_04