Substituted 3-amino

The isoxazoline ring is also readily cleaved by such reducing agents as do not affect the isoxazole ring. Thus, for example, the treatment of isoxazolines (186) with LiAlHj proceeds with a smooth cleavage of the heterocyclic ring to form substituted 3-amino-propan->l-ols... 

Despite the lability of the N — O bond, addition of organomctallic reagents to 5-substituted isoxa-zolines provides a potential route for stereoselective synthesis of substituted 3-amino alcohols1. 

Casanola-Martin GM et al. (2006) New tyrosinase inhibitors selected by atomic linear indices-based classification models. Bioorg Med Chem Lett 16(2) 324-330 Tan CY, Wainman D, Weaver DF (2003) N-, alpha-, and beta-substituted 3-amino-propionic acids design, syntheses and antiseizure activities. Bioorg Med Chem 11(1) 113-121... 

During the asymmetric synthesis of erythro and threo a-substituted 3-amino esters, the dimethylbinaphthyl moiety (28 in Fig. 4.5) was removed using transfer hydrogenolysis. 

Reaction of the substituted 3-amino-2-methylaminopyrimidin-4-one 200 with acetic anhydride gives rise to the tricyclic heterocyclic system 201 in good yield (Equation 52) <1995MI445>. 

Thus oxidation of both 6- and 7-substituted 3-amino-benzo-l,2,3-triazin-4-ones with lead tetraacetate in methanol produced a mixture of p- and m-substituted benzoates, clearly indicating that a symmetrical intermediate, i.e. benzocyclopropenone (166) was formed and underwent ring opening by attack of solvent121 ... 

A variation using thioacylguanidines affords 5-substituted-3-amino-l,2,4-thiadiazoles. If an amidinothiourea is oxidized, 5-amino-l,2,4-thiadiazoles are obtained. A recent example of this type of synthesis has been reported the amidinothiourea 87 was oxidized to the 1,2,4-thiadiazolium salt 88 on treatment with bromine (Equation 25) <2003SC2053>. 

Cyclocondensation between substituted /3-amino alcohols and carbonyl derivatives 184... 

Spickett and Wright investigated the reactions of 4-substituted 3-amino-1,2,4-triazoles and EMME in acetic acid for 24-48 hr [67JCS(C)503]. Generally, they obtained [l,2,4]triazolo[l,5-a]pyrimidine-7-ones (1124) in 38-56% yields. In the case of the benzyl derivative (R = CH2Ph), the isomeric triazolo[l, 5-a]pyrimidin-5-one (1125) was also isolated from the mother liquor, in 5% yield. From the 4-ethyl and 4-phenethyl derivatives (R = Et, CH2CH2Ph), l-(l,2,4-triazol-3-yl)pyridin-2-ones (1126) were also obtained in 1-2% yields. 

On the way to the investigation of the structure-activity relationship Huang et al. [138] performed the MCRs involving diverse-substituted 3-amino-l,2,4-triazoles,... 

A -Chloro derivatives of amidines, isoureas and guanidines react with potassium 5-methyl-cyanodithioiminocarbonate (266) to yield 2,5-substituted 3-amino-1,2,4-thiadiazoles (Equation (37))... 

Several of the well known cyclization reactions of aromatics that are used for the preparation of benzoheterocycles also work for pyridines (66AHC(6)229). 3-Aminopyridine undergoes the Skraup reaction (equation 59), and the substituted 3-amino derivative (97) undergoes intramolecular Friedel-Crafts reaction (equation 60). Further examples of these reactions can be found in the appropriate part of Chapter 2.06. 

Amino acids are useful precursors for the construction of 3-peptides,2,3 a-substituted 3-amino acids4 and related compounds.5 They can be prepared enantiomerically pure by homologation of a-amino acids using the Amdt-Eistert method. 

Cyclization of a 1-substituted 3-amino-5-pyrazolone or its 5-amino isomer produces 2- or 1-substituted pyrazolo[3,4-b]pyridones, respectively. Alternative reaction at N-2 to form a pyrimidine ring has not been reported. 

Oxidation of methyl ketone guanylhydrazones (686) with selenium dioxide affords the corresponding monosubstituted glyoxal derivatives (687) which cyclize to the 5-unsubstituted 3-amino-1,2,4-triazines (473) (78HC(33)189, p.360). We have already noted the cyclization of bis(alkylidene)- or bis(arylidene)-acetone guanylhydrazones (475) in the synthesis of 6-(vinyl-substituted) 3-amino-1,2,4-triazines (477) (Section 2.19.4.1.1). 

Lactams substituted only in the 3 position cannot be prepared by the present procedure, since the lactam formed has the nitrogen of the chlorosulfonyl isocyanate attached to the more highly substituted carbon atom of the olefinic double bond in Markownikoff fashion. 2-Azetidinones substituted in the 3 position only have been prepared by Grignard reagent-catalyzed cyclizations of esters of appropriately substituted /3-amino acids.4,5... 

Lactam structures have been reported to be constructed by treatment of substituted (3-amino acids with dicyclohexylcarbodiimide (DCC) in refluxing acetonitrile (Scheme 98), [218]. The substrates were prepared by a multistep synthetic protocol previously reported [219]. 

The intramolecular Heck reaction (type d cyclization) has been used to access 3-benzazepine derivatives from o-bromobenzyl substituted /3-amino ester precursors in excellent yields. A key feature though was the use of microwave irradiation in the poly(ethylene glycol), PEG3400, as the solvent <2007EJ0201>. 

Imidazopyridodiazepines 56 are formed by />m-annulation of imidazo[l,2- ]pyridines 55 (route a Scheme 8 Table 7) <2002TL9119>. These compounds can alternatively be synthesized directly from the 2-substituted-3-amino imidazopyridines 54 and simple aldehydes or a,/3-unsaturated aldehydes in good yields. Products are formed as cis//rans-m xtutes. 

The 4 + 2-cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosoben-zene produces [2.2.2]bicycloadducts, which are readily reduced by alane to trans-2-substituted 3-amino-l,2,3,6-tetrahydropyridines stereospeciflcally.123 The intramolec- (g) ular nitroso-Diels-Alder reaction of a-acetoxynitroso derivatives in aqueous medium produces 3,6-dihydro-l,2-oxazines in high yield.124 The nitroso-Diels-Alder reaction of acyclic OTIPS-dienes (115) and 6-methyl-2-nitrosopyridine (114) in the presence of (g) [Cu(MeCN)4(difluorosegphos)]PF6 yielded the dihydro 1,2-oxazine cycloadduct (116) with high yield and enantioselectivity (Scheme 33). 125 (Fe)... 

A three-step reaction sequence starting from /3-amino alcohol 212 has been utilized in the synthesis of 2-cyanoazetidine (Scheme 42) <2002TA297, 2006SL78>. The A-benzyl-substituted /3-amino alcohol was first N-cyanomethylated to give the corresponding A-benzyl-A-cyanomethyl /3-amino alcohol 213. The latter compound was stereoselectively transformed into chlorinated amine 214 using thionyl chloride. An intramolecular alkylation of... 

Both substituted 3-amino-2//-l-benzothiopyrans <1995EP648741> and 4-acyl-4-hydroxy-2//-l -bcn/othiopvrans <2001W02001087879> inhibit thrombin activity and thus behave as anticoagulants and 4-(SCH2CONR2) derivatives of 3,4-dihydro-2//-l-benzothiopyran 1-oxide have been claimed as treatments for excessive sleepiness and fatigue <2005USP2005228040>. 

V-Chloro derivatives of amidines, isoureas and guanidines react with potassium 5-methyl cyanodithioiminocarbonate (320 R = Me) to yield thiadiazole systems of type (324 Scheme 114) (75BCJ310 73CL917). A related transformation occurs when the cyanothioiminocarbon-ates (322) and chloramine are allowed to condense at low temperature (76EGP119791). In this manner a variety of 5-substituted 3-amino-l,2,4-thiadiazoles (325) are obtained in good yields (Scheme 115). The use of ethoxycarbonylthioiminocarbonates (326) in this... 

The regiospecific alkylation of aspartate enolates provides a valuable basis for the stereocontrolled access to a-substituted /3-amino acid derivatives454,455. The nature of the cation appears to control the geometry of the enolate, as established by trapping experiments the E(O) enolate prevails for the lithium cation, while the Z(O) enolate is the current isomer for potassium456. Thus, high diastereoselectivities could be achieved... 

The same opinion is held by Hauser and coworkers for the condensation of the ketoaminonitriles 72 with acetophenone in the presence of the polyphosphoric acid66. They assume an initial conversion of precursors 72 into ketoaminoamides 73, which are then condensed with the ketone to give substituted 3-amino-2-pyridones 74 (equation 27). 

Naphtho[2, 3 3,4]-[l,2,5]triazocino[8,l+]quinazolinone 137 was obtained by refluxing of 2-substituted 3-amino-quizalin-4-one with 2,3-dichloro-l,4-naphthoquinone in DMF (Scheme 35 <2001MOL267>). Initial formation of 5,6-dihydrotriazocine derivative was followed by elimination of arylsulfinic acid and formation of ring system 137. 

From the results of 4H NMR studies14 and X-ray analysis of 712 the conclusion was drawn that the ground state of substituted 3-amino-benz[d]isothiazole-1,1-dioxides is best represented by structures (7a) and (9a). 

The reaction of monosubstituted glyoxals (455) with aminoguanidine (460a) has been extensively studied. Either 5- or 6-substituted 3-amino-1,2,4-triazines can be obtained depending on the reaction conditions. N-Alkyl-substituted aminoguanidines with 1,2-dicarbonyl compounds condense to give 3-alkylamino-l,2,4-triazines, while... 

Oxidation of several 2-substituted 3-amino-4(3//)-quinazolinones with lead tetraacetate at — 20 °C in dichloromethane gives solutions of 3-acetoxyaminoquinazolinones 7, which azirid-inate alkenes via a mechanism similar to that involved in the epoxidation of alkenes with peroxyacids3,26,33. The aziridination with preformed 7 is potentially useful for alkenes sensitive to oxidants. 

Meng J, Kung PP (2009) Rapid, microwave-assisted synthesis of Nl-substituted 3-amino-... 

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