An orally active, water-soluble neurokinin-1 receptor antagonist suitable for both intravenous and oral clinical administration

1-(5-{[(2R,3S)-2-({(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-f luorophenyl)morpholin-4-yl]methyl}-2H-1,2,3-triazol-4-yl)-N,N-dimethylmetha namine hydrochloride 3 is a high affinity, orally active, h-NK1 receptor an tagonist with a long central duration of action and a solubility in water o f > 100 mg/mL. The construction of the 5-dimethylaminomethyl 1,2,3-triazol- 4-yl unit, which incorporates the solubilizing group of 3, was accomplished by thermal rearrangement of a propargylic azide in the presence of dimethy lamine. Compound 3 is highly effective in pre-clinical tests that are relev ant to clinical efficacy in emesis and depression.