7- Aminomethyl-2-substituted

Amino group of 7-aminomethyl-2-substituted perhydropyrido[l,2-u]pyr-azines were reacted with 2-bromopyridine and 2-chloropyrimidines to give 7-(hetarylamino)methyl derivatives in the presence of Na2C03 in DMF at 100-120°C for 18h in 13-51% yields (00MIP15). An aminomethyl group of... 

Chiral alkoxy- and aminomethyl-substituted a-allylsilyl carbanions have been reacted with aldehydes to give 1-silylhomoallylic alcohols with high y-regioselection and ii-stereoselection, and moderate to good deJ ... 

Silyl homoallylic alcohols are obtained with high y-regioselection and E-stereoselection on reaction of chiral alkoxy- and aminomethyl-substituted a -silylallyl carbanions with aldehydes factors which influence the diastereomeric excess have been identified. 

Aminomethyl substituted pyrrolo-benzdiazepine can be formed from the Cbz-protected precursor 214 and further reduced into tetrahydro derivative 215. Alternatively, the unsubstituted ring in 217 has been synthesized by a Bischler-Napieralski method (Scheme 45 (1993JHC749). 

A pyrrole synthesis leading to 20 has been achieved by a CuBr catalyzed cyclization of the intermediate imine 21, which was prepared over several steps from 1,3-hexadiyne (22) in a one-pot operation <02CHE748>. Aminomethyl substituted allenes have also been used for the synthesis of pyrroles by a palladium catalyzed annulation with aryl iodides <02H(57)2261>. 

Reacting dichlorocarbene with aminomethyl-substituted azines 529 and 530 provides access to imidazo[l,5-a]pyridine and imidazo[5,l-a]isoquino-line in moderate yields, even though dichlorocarbene is not the reactant of choice for such transformations (91JOC2400). 

Cooper, A.B., J.J. Wright, A.K. Ganguly, J. Desai, D. Loenberg, R. Parmegiani et al. (1989). Synthesis of 14-a-aminomethyl substituted lanosterol derivatives inhibitors of fungal ergosterol biosynthesis. J. Chem. Soc., Chem. Commun. 898-900. 

Phthalimidomethyl-substituted 477-pyrido[4,3-( ]-l-thia-2,4-diazine 1,1-dioxide derivative 125 undergoes hydrazino-lysis to produce the (7-3-aminomethyl-substituted product, which is then acylated to yield the amido adducts 126 (R = H, Ph R =Ar, NHAr) as potential cholecystokinin/gastric receptor ligands (Equation 17) <1997BSB781>. Similar acylation chemistry has been applied to the synthesis of related 5-(methylamides) of 2/7-benzo-l-thia-2,4-diazine 1,1-dioxides (see Section 9.05.9.1.3) <2001CHE237>. 

Lin J, Rajaram AR, Pu L (2004) Enantioselective fluorescent recognition of chiral acids by 3-and 3,3 -aminomethyl substituted BINOLs. Tetrahedron 60 11277-11281... 

Thermoplastic molding compositions, containing aminomethyl-substituted poly-(phenylene ethers), epoxy group containing ethylene copolymers, and aromatic polycarbonates, have been produced [271]. 

Ethyl oleate was examined in non-isomerizing HAM with a variety of primary and secondary amines to produce mainly 9- or 10-aminomethyl-substituted stearic acid esters (Scheme 5.100) [87]. With the exception of diisopropylamine, almost excellent yields were achieved. When an excess of the fatty acid ester with regard to the amine (hexylamine) was used, two oleo compounds could be linked via an... 

In strong contrast to 1,4-diene [86], the corresponding divinylsilanes (X = Si) produce aminomethyl-substituted silacyclohexanes via a hydroformylation-aldol condensation-reductive amination pathway (Scheme 5.110) [94]. In case of R H, in the final product both substituents adopt trans geometry to each other. Such silacyclohexanes display spasmolytic and antiarthritic activity. 

Figure 9.2. Structure of the aminomethyl substituted tetraphenylporphyin Sn(lV) complexes.

Compounds 33b, 34 with the amino group attached to the spiropyrrolidine or cyclopropyl-substituted pyrrolidine fragment proved to exhibit broad spectrum of antibacterial activity (Scheme 18) [124-129]. Aminomethyl substituted pyrrolidines and their heterocyclic derivatives were incorporated into position 7 of fluoroquinolone [130-132]. Optically active derivatives of 7-(3-hydroxypyrro-lidin-l-yl)-6-fluoroquinolones have been shown to be promising antibacterials [133-135]. 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

Table 3 gives the corresponding physical properties of some commercially important substituted pyridines having halogen, carboxyHc acid, ester, carboxamide, nitrile, carbiaol, aminomethyl, amino, thiol, and hydroxyl substituents. 

For a viable commercial process, the selection of materials and the choice of synthetic route is governed primarily by cost, not by overall yield. The selection of starting material is dictated usually by the desked C-3 substituent. For cephalosporins containing 3-acetoxymethyl or 3-(substituted)methyl such as 3-thiomethyl and 3-aminomethyl derived moieties, the most dkect synthetic route is from cephalosporin C, whereas pencillin V or G is the preferred starting material for the synthesis of the C-3 methyl cephalosporins. The three chemical transformations (2), (5), and 6) can potentially be carried out in a variety of ways, the precise sequence being determined by a balance of competing factors such as cost and optimization of yield (87). 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

An important extension of these reactions is the Mannich reaction, in which aminomethyl-ation is achieved by the combination of formaldehyde, a secondary amine and acetic acid (Scheme 24). The intermediate immonium ion generated from formaldehyde, dimethyl-amine and acetic acid is not sufficiently reactive to aminomethylate furan, but it will form substitution products with alkylfurans. The Mannich reaction appears to be still more limited in its application to thiophene chemistry, although 2-aminomethylthiophene has been prepared by reaction of thiophene with formaldehyde and ammonium chloride. The use of A,iV-dimethyf (methylene) ammonium chloride (Me2N=CH2 CF) has been recommended for the iV,iV-dimethylaminomethylation of thiophenes (83S73). 

Halogenomethyl, hydroxymethyl and aminomethyl groups readily undergo displacement reactions with nucleophilic reagents. Both side-chain and nuclear substitution products have been obtained (Scheme 57). These two possibilities are exemplified by the reaction of furfuryl chloride with sodium cyanide (Scheme 58). 

---