Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 1,1-Dimethylethyl 4-[5-[[methyl[(1R)-1-phenylethyl]amino]carbonyl]-2-thiazolyl]-1-piperazinecarboxylate

Participants

Reaction Steps

1-(1,1-Dimethylethyl) 4-(5-carboxy-2-thiazolyl)-1-piperazinecarboxylate (i.e. the product of Example 4, Step B) (1.0 g, 3.2 mmol) was suspended in 10 mL of dry acetonitrile and treated with triethylanaine (892 μL, 6.4 mmol) to give a homogeneous solution. To this was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.33 g, 3.5 mmol) followed by (α,R)—N,α-dimethylbenzenemethanamine (i.e. the product of Example 1, Step C) (200 μL, 1.38 mmol). The reaction mixture was stirred at ambient temperature for 3 days, concentrated under reduced pressure, diluted with ethyl acetate, washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate and concentrated under reduced pressure to give 1.38 g of an orange foam. Purification by silica gel chromatography using an ethyl acetate/hexanes gradient from 1:9 to 100:0 gave 0.78 g of the title compound as a yellow solid.

Provenance & Evidence