1,2-Dichloroethane → 3-((3S,9aS)-8-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetyl)-octahydropyrazino [2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

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Reaction Steps

6-Fluoro-2-methyl-3-((3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)benzonitrile 2,2,2-trifluoroacetate (1.06 g, 2.71 mmol) was suspended in DCM (20 mL) and TEA (1.13 ml, 8.13 mmol) was added. The mixture was stirred for 5 min and then 2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetic acid (0.555 g, 2.71 mmol), HOBT (0.623 g, 4.07 mmol) and EDC (1.039 g, 5.42 mmol) were added and the mixture was stirred for 4 h. The reaction mixture was poured into brine/NaHCO3 mixture. The DCM layer was separated and dried over Na2SO4, then was filtered and concentrated. The residue was purified by chromatography using a 120 g ISCO Redisep column eluting with a 5% (NH4OH: MeOH 1:9)/95% DCM solvent system to yield 3-((3S,9aS)-8-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetyl)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile: LC-MS: M+1=463.

Provenance & Evidence