Diisopropylethylamine → (S)-tert-butyl 3-bromo-1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

関与物質

役割	名称	HCID	仕込み量
反応物	Diisopropylethylamine	HCID 81531	—
反応物	(2S)-2-Amino-N,3,3-trimethylbutanamide	HCID 445856	—
反応物	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
反応物	3-bromo-7-[(tert-butoxy)carbonyl]-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1-carboxylic acid	HCID 57635428	—
溶媒	Water	HCID 962	—
溶媒	Dimethylformamide	HCID 6228	—
生成物	(S)-tert-butyl 3-bromo-1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate	HCID 57635359	80.4%

反応手順

Acid Intermediate 1I (0.62 g, 1.79 mmol) was dissolved in DMF and L-tert-Leucine methylamide (0.31 g, 2.14 mmol) was added followed by DIEA (0.94 mL, 5.37 mmol). The resulting mixture was stirred for 20 minutes, HBTU (0.75 g, 1.97 mmol) was added in one portion and the mixture was stirred overnight. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water, then brine, and dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by normal phase chromatography, eluting with a 0-10% methanol/DCM gradient to provide product Intermediate 1J as an off-white solid (0.68 g, 80%).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08859538B2
出典データセット	uspto-grants-2014_10
ORD ID	ord-26976d8d425d4c809432bbdffcfe8ef0
出典メモ	uspto-grants-2014_10