Tris(hydroxymethyl)aminomethane → HCID 86612294, compound

Participants

Reaction Steps

(1R,3S)-N-{3-[1-(2-Amino-ethyl)-piperidin-4-yl]-5-methoxy-6-methyl-isochroman-1-ylmethyl}formamide was obtained by distributing the dihydrochloride between aqueous sodium hydroxide and dichloromethane and then evaporating the organic phase. To a mixture of IRA-67 (1.2 g) and (1R,3S)-N-{3-[1-(2-amino-ethyl)-piperidin-4-yl]-5-methoxy-6-methyl-isochroman-1-ylmethyl}formamide (0.3 g, 0.69 mmole) add chloroform (12 mL) and 4-fluorobenzoyl chloride (0.310 g, 1.95 mmole) in chloroform (2 mL). After 24 hours add additional 4-fluorobenzoyl chloride (0.3 g, 1.89 mmole) and IRA-67 (2 g). After an additional 18 hours add PS-trisamine (1.0 g of 3.75 mmole/g) and stir for 6 hours. Filter and concentrate, then flush the product over a 35 g silica gel cartridge (eluting with ammonium hydroxide:methanol:ethyl acetate 1:4:95). Collect the appropriate fraction and concentrate to obtain the title compound. CIMS 484, tR (min)=0.46.

Provenance & Evidence