Diisopropylethylamine → rac-2,6-Dimethyl-N-(7,7,7-trifluoro-2-hydroxy-2-methylheptan-3-yl)-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo[1,2-a]pyridine-3-carboxamide

150 mg (0.390 mmol) of 2,6-dimethyl-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo[1,2-a]-pyridine-3-carboxylic acid Example 91A and 163 mg (0.429 mmol) of HATU were initially charged in 2 ml of DMF. 0.2 ml (1.17 mmol) of N,N-diisopropylethylamine and 101 mg (0.429 mmol) of rac-3-amino-7,7,7-trifluoro-2-methylheptan-2-ol hydrochloride Example 103A were then added, and the mixture was stirred at RT overnight. 10 ml of water were added, the reaction solution was extracted twice with 20 ml of ethyl acetate and the combined organic phases were washed with 20 ml of water and with 20 ml of sat. aqueous NaCl solution, dried over MgSO4, filtered and concentrated. The residue was purified by preparative RP-HPLC (ACN:water+0.1% HCOOH). The product fractions were combined and concentrated to dryness and the residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water and lyophilized overnight. This gave 91 mg of the target compound (98% pure, 40% of theory).

1. extractionthe reaction solution was extracted twice with 20 ml of ethyl acetate
2. washthe combined organic phases were washed with 20 ml of water and with 20 ml of sat. aqueous NaCl solution
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by preparative RP-HPLC (ACN:water+0.1% HCOOH)
7. concentrationconcentrated to dryness
8. dissolutionthe residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water
9. waitlyophilized overnight

ORDレコード

ord-87a562c06d454a90810b993a68c78141

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08946215B2