Diisopropylethylamine → 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(prop-2-ynylamino)ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxamide

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	2-amino-N-(prop-2-yn-1-yl)acetamide hydrochloride	HCID 47002635	—
反応物	3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid	HCID 71471635	—
溶媒	Dichloromethane	HCID 6344	—
生成物	3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(prop-2-ynylamino)ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxamide	HCID 71468069	88.9%

反応手順

Stir a mixture of 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid (0.8 g, 1.7 mmol), N,N-diisopropylethylamine (663 mg, 5.1 mmol), 2-amino-N-(prop-2-yn-1-yl) acetamide hydrochloride (305 mg, 2.0 mmol) and HATU (974 g, 2.6 mmol) in CH2Cl2 (10 mL) at room temperature for 2 hours. The reaction mixture is diluted with CH2Cl2 (40 mL) and is washed with water (10 mL×3) and brine. Then the organic layer is dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by preparative HPLC to afford 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(prop-2-ynylamino)ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxamide as a white solid (850 mg, 88.4%). MS (m/z): 584.1 (M+Na).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08648081B2
出典データセット	uspto-grants-2014_02
ORD ID	ord-089254a121594c83be3ee0b0cd122afb
出典メモ	uspto-grants-2014_02