Aminosulfonamide

Methylation of nitrogen at the 2 position also proves to be consistent with diuretic activity. Condensation of 160 with urea affords the heterocycle, 193. Treatment of this compound with methyl iodide and base effects alkylation on the more acidic ring nitrogen (194). Basic hydrolysis then gives the N-methylated aminosulfonamide (195). Condensation of this with chloroacetalde-... 

The Ley group also investigated the PS-base/tosyl chloride methodology developed by Brain (see above. Scheme 8) for the synthesis of 2-aminooxadiazoles from semicarbazides, especially with a view to directly synthesize 2-aminosulfonamide substituted 1,3,4-oxadiazoles, a compound class of interest for agrochemical and pharmaceutical apphcations (Scheme 10) [71]. In this case, the choice of the supported base was crucial for the result of the reaction weak bases (PS-DIEA, PS-NMM) could still afford the cyclized 2-aminooxadiazole product, but could not efficiently... 

Scheme 1.64 Cu-catalysed allylic substitution of cinnamyl phosphate with ZnEt2 in the presence of P-aminosulfonamide ligands.

Scheme 23 Decomposition Pathways of (a) an a-Aminosulfonic Acid and (b) an a-Aminosulfonamide[1051...

There are several routes to 3,4-dihydro-2/f- 1,2-benzothiazine dioxides (158), including the cyclization of aminosulfonic acids (157) or cyanosulfonamides (159). 3,4-Dihydro-IH-2,1-benzothiazine dioxides (161) are normally prepared by thermolysis of the sodium sulfonates (160) or aminosulfonamides (162) (71CB1880), and l//-3,4-dihydro-2,3-benzothiazine dioxides (164) are available either by a Pictet-Spengler cyclization of sulfonamides (163) with trioxane or of sulfonamide acids (165) with polyphosphoric acid (76CC470). 

Because sulfonamides are generally more stable towards enzymatic degradation than amides, the preparation of oligosulfonamides as peptide mimetics has been thoroughly investigated. The synthesis of a-aminosulfonamides has not been successful, probably because of the instability of this class of compound [261], For the more stable P-amino sulfonamides and vinylogous a-aminosulfonamides (3-amino-l-pro-pene-l-sulfonamides), however, suitable synthetic routes have been developed. Unfortunately, the preparations of the required monomers are not as easy as those of related amino acid derived monomers (Figure 16.27). 

Chiral palladium complexes have been employed as enantio- and diastereo-selective catalysts of a Mannich-type addition of /3-kclo esters to aldimines and imino esters, q. in a strategy which activates both reactants 28 anti-Selective direct enantioselective Mannich reactions use a BINAP-derived axi- ally chiral aminosulfonamide as organocatalyst.29... 

The ethyl acetate solution containing aminosulfonamide (ca. 27.9 g, 86 mmol 95 5 trans/cis) from step 5 was concentrated by distillation (1 atm) to a volume of 70 mL. Acetone (250 mL) was added and the concentration repeated to a volume of 70 mL. The operation was repeated, this time concentrating to a volume of 160 mL. Maleic acid (9.98 g, 86 mmol) was added. The mixture was stirred until the salt crystallized, and was then stirred for 12-18 h at 20°-22°C. The mixture was filtered, and the product cake washed with acetone (1 bed volume). The product was air-dried, then dried in vacuo (100 mBar, nitrogen sweep, 75°C) to constant weight. Yield 33.0 g (92%) of the maleate salt as a white crystalline solid. HPLC 99 1 trans/cis (above method). 

A mechanically stirred suspension of crude amino-sulfonamide hydrochloride salt (26.4 g, 73 mmol) in water (70 mL) was heated at 90°-95°C until all of the solid dissolved. To the hot solution was added activated carbon (Darco KB, 0.26 g), and the mixture stirred for 15 min at 90°-95°C. The mixture was filtered hot (85°-90°C) through a well-washed bed of filter aid (SuperCel). The filter cake was washed with boiling water (9 mL). The filtrate and cake wash were combined, and the product allowed to crystalize as well-stirred solution was cooled to 60°C. The mixture was stirred for 1 h at 60°C, or until the product had convened to the thermodynamically more stable hemihydrate crystal form. The mixture was then slowly cooled to 3°C, and then stirred for 1 h at this temperature. The mixture was filtered cold, using the mother liquors to rinse the cake. The product was air-dried, then dried in vacuo (100 mBar, nitrogen sweep, 45°-50°C) to constant weight. Yield 24.2 g (92% yield 59% overall yield from hydroxysulfone) of pure aminosulfonamide hydrochloride salt (dorsolamide) as a white crystalline solid. HPLC 99.9 area % (254 nm), 99.6 wt % vs an external standard, >99% (4S,6S) as the N-TFA derivative. Specific Rotation a589 =-17.1° (c=1.00, H20). MP 238°C. 

Reaction of pyridine-derived aminosulfonamides 489 and 491 with urea or guanidine gives access to the fused 1,2,4-thiadiazine 1,1-dioxides 490 (Scheme 256) and 492 (Scheme 257), respectively <1999T5419, 2002JME90, CHEC-III (9.05.9.2.3)331>. 

Interesting chiral water-soluble aminosulfonamide ligands containing a phenyl-sulfonic acid substituent have been synthesized and engaged directly with a ruthenium precursor to reduce enantioselectively aromatic ketones to the corresponding alcohols [84]. As concluded by the authors, these ligands should be evaluated in bi-phasic catalysis. 

Cyclization of 2-aminoarenesulfonamides with carbonyldiimidazole in dioxan affords 2//-1,2,4-benzothiadiazin-3(4//)-ones <88EUP268990>. An interesting adaptation of this method involves the carbonylation of / -aminosulfonamide (227) with carbonyldiimidazole to yield the 5,6-dihydro-2/f-... 

Acid-catalyzed reaction between 4-substituted 2-aminosulfonamides 215 (R = H, Me, Cl) and 2-bromomethyl-l,3-dioxolane provides access to 3-(bromomethyl)-benzo-l-thia-2,4-diazine 1,1-dioxide 216 (Equation 48). Related compounds have been used as precursors to 3-(A -alkyl) derivatives as potential ligands for and S-HTja receptors (see Section 9.05.7.7) <2005BML1185>. 

Orthoformates react with pyrido aminosulfonamides such as 230 to produce the corresponding 4//-l-thia-2,4-diazine 1,1-dioxides 231 (R = H, Me) (Equation 54) <1998JME2946, 2003S1603>. These compounds ate reduced readily to the 3,4-dihydro-2/7-pyrido-l-thia-2,4-diazine 1,1-dioxide derivatives (see Section 9.05.6.2.4), which are of significant interest as positive allosteric modulators of AMPA receptors <2001W02001040210, 2004ERP2854634>. 

Fusing urea or guanidine with pyridine-derived aminosulfonamides gives access to 2//-pyrido-1-thia-2,4-diazine-3(47T)-one 1,1-dioxides and 3-amino-4/7-pyrido-l-thia-2,4-diazine 1,1-dioxides, respectively. Thus, 4-aminopyridine-... 

The reactions between various benzene- and pyridine-derived aminosulfonamides 248 and l.l -thiocarbonyldi-imidazole have been studied in detail. For 2-amino-A -methylbenzenesulfonamide (X = Y = C, R= H, R = Ph) and a... 

In 2009, the Maruoka group used the previously discussed aminosulfonamide catalyst 39b to facilitate the reaction of various aldehydes 2 with A -Boc-protected imines 23a-b, 23m to afford the Ai-Boc-protected anh-P-amino-P-aryl aldehyde 40a-f in high yield and anti-selectivity and excellent ee (Scheme 5.22) [30],... 

Maruoka s axially chiral aminosulfonamide 119 catalyzes the cross-aldol reaction between two aldehydes, affording aldols with highly diastereo- and enantioselectivity [145]. Low catalyst loading and short reaction times (Ih) make this procedure very attractive for the formation of C-C bonds (Charts 3.16 and 3.17). Unfortunately the yields are low for less reactive aromatic aldehydes. 

The same group reported shortly after the use of potassium bisulfite as a convenient equivalent of sulfur dioxide for the coupling with aryl iodides or bromides and hydrazines. A wide range of aryl A-aminosulfonamides were prepared in good yields using Pd(OAc)2/PtBu3 as the catalyst [43]. 

Palladium-catalyzed aminosulfo-nylation of aryl halides, (b) E. J. Emmett, C. S. Richards-Taylor, B. Nguyen, A. Garcia-Rubia, B. R. Hayter, M. C. Willis, Org. Biomol. Chem. 2012,10,4007 014. Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides scope of the three-component synthesis of A-aminosulfonamides. 

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