4-Hydroxy-2-methyl-3(2H)-isothiazolone-1,1-dioxide as protecting group of 4-(N-methylaminosulfonyl)methylphenylhydrazine during Fischer indole synthesis

Synthesis of tryptamines by the Fischer method using synthetic precursors and latent forms of amino-butanal (review)

“…The formation of alkylation products 58 [261,262,240], including high-molecular polymers 59 [262] and other side products, is therefore possible under the conditions of the Fischer reaction, and they greatly complicate the isolation of the desired tryptamines. In order to suppress the formation of the condensation products it is possible to use hydrazines with a sulfamide group in the latent isothiazolone form [261] or protected by an ethoxycarbonyl group [234] in the Fischer reaction. This facilitates purification, and the protecting groups are then easily removed in an alkaline medium.…”

An analytical perspective on favoured synthetic routes to the psychoactive tryptamines

“…7A) [61]. This one-pot approach, however, has also resulted in acid-induced degradation followed by the formation of di-or multimeric by-products (61)(62)(63) under these conditions (Fig. 7B-D).…”

“…7B-D). Structure elucidations of these were performed to a different extent by IR, NMR and exact mass measurements [62][63][64]. The main 2,5-bisindole Sumatriptan impurity (64) that occurs during a typical Fischer indolisation has recently been synthesised.…”

“…(B) The use of a hydrazine and an acetal for indolisation. A dimeric side product (61) was observed[62] (C) Formation of a multimeric side product (62) using a two-phase indolisation procedure[63]. (D) 1,1-bis(indol-2-yl)-4-dimethylaminobutane by-product (63)[64].…”

An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT1D Receptor Agonist

“…The indole portion of avitriptan has been prepared by a zinc chloride-catalyzed Fischer indolization of hydrazine 6 with dihydropyran, 7 , to give the hydroxypropylindole 8 (Scheme ); by a more convergent route in which the B and C subunits were combined to form diethyl acetal 10 and then reacted with 6 in a Fischer indolization to give 1 directly (Scheme ); and by a palladium-catalyzed heteroannulation reaction of iodoaniline 12 with silylalkyne 13 (Scheme ) …”