Diisopropylethylamine → 8-(2-Ethoxycarbonyl-indan-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

To a solution of 3,4-dihydro-1H-isoquinoline-2,8-dicarboxylic acid 2-tert-butyl ester (2.0 g, 7.2 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (1.5 g, 7.2 mmol), HATU (3.3 g, 8.6 mmol) in anhydrous DMF (70 mL) is added DIPEA (1.4 mL, 8.6 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (150 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (200 g silica gel, gradient elution: 5-50% EtOAc in heptane) to give a pure product (217) as white solid (3.3 g, 99%).

1. customAfter the removal of DMF in vacuo
2. dissolutionthe residue is dissolved in EtOAc (150 mL)
3. washwashed with water (1×10 mL) and brine (2×10 mL)
4. dry with materialThe organic layer is dried over anhydrous Na2SO4
5. concentrationconcentrated in vacuo
6. customThe residue is purified by flash column chromatography (200 g silica gel, gradient elution: 5-50% EtOAc in heptane)

ORD record

ord-0b3154918832476faa53eea71894971f

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569535B2