Diisopropylethylamine → 2-[(5-Chloro-benzo[b]thiophene-3-carbonyl)-amino]-indane-2-carboxylic acid ethyl ester

To a 40 mL vial containing a stirring bar, 5-chloro-benzo[b]thiophene-3-carboxylic acid (518 g, 2.44 mmol) is charged with dry DCM (7 mL). Stirring is initiated. HBTU (922 mg, 2.43 mmol) and DIPEA (0.95 mL, 8.0 mmol) are added. Then 2-aminoindane-2-carboxylic acid ethyl ester (500 mg, 2.44 mmol) is added. The reaction is allowed to stir for 20 h. Analysis by tlc of the reaction mixture (silica, 10% MeOH/DCM) indicates complete consumption of the starting amine. The contents of the reaction flask are diluted with EtOAc (50 mL) and transferred to a separatory funnel. This is washed consecutively with dilute aqueous NaHCO3 (25 mL) and brine (25 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 1.64 g of off white solid. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 20% EtOAc in heptanes over 3 column volumes followed by a linear gradient to 50% over 8 column volumes and then 90% EtOAc for 2 column volumes with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 7 through 31 are combined and evaporated in vacuo. Pumping to a constant weight gives amorphous white solid 0.94 g.

1. additionTo a 40 mL vial containing a stirring bar
2. stirringto stir for 20 h
3. customconsumption of the starting amine
4. additionThe contents of the reaction flask are diluted with EtOAc (50 mL)
5. customtransferred to a separatory funnel
6. washThis is washed consecutively with dilute aqueous NaHCO3 (25 mL) and brine (25 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated in vacuo
10. customto provide 1.64 g of off white solid
11. customThis material is purified
12. custom25 mL fractions are collected
13. customevaporated in vacuo

ORDレコード

ord-b2b9bcd6184441eb826717ae6c4d056f

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08569535B2