Alkylamino-substituted

Alkylamino-substituted furazans can be obtained by reduction of acylamino derivatives. The chlorine atom at the side chain may be replaced with a nucleophile (Scheme 114) (85MI1, 88AP77, 89AP579, 89MI1, 92AP151). 

Typically, the 1,4-(oxa/thia)-2-azole ring system does not exist in tautomeric forms. However, in some cases discussed in CHEC-II(1996), the 3-alkylamino-substituted 1,4,2-dithiazole-l-oxides may exist in tautomeric forms with the contribution of alkylamino substituents <1996CHEC-II(4)506>. 

Starch ethers having amino groups in the side chain are produced by alkylation with either co-chloroalkylamines or alkylamino-substituted alkylenes. 

For example, the new etoposide analog GL-311, possessing a C-4/ -aminoaniline substitution, is currently in phase II clinical trials for various anticancer treatments. This compound is a more potent inhibitor of proliferation of refractory cancer cells than etoposide [34]. Attempts to increase the biological activity of GL-311 by di- and tri- substitution of the aniline ring have produced derivatives up to 10 times as potent as etoposide [35]. Other such compounds have proved at least as active as etoposide as anticancer agents these include alkylamino-substituted derivatives [36, 37] and synthetic acetyl salicylic acid, 2-... 

Extending the intermolecular coupling, dihydroindoles (Scheme 4), dihydroquinolines, and other N-heterocycles were successfully synthesized by simple intramolecular trapping reactions, starting from alkylamino substituted aryl bromides. [8] Intramolecular amination can be achieved in the presence of tetrakis(triphenylphosphine)palladium as catalyst and stoichiometric amounts of base in toluene. Here, best results are obtained with mixtures of NaOtBu and potassium carbonate. 

Walczak C, Payne TJ, Wade CB, Yonkey M, Scheid M, Badour A, Mohanty DK (2015) The thermal instability of 2,4 and 2,6-/V-alkylamino-disubstituted and 2-/V-alkylamino-substituted nitrobenzenes in weakly alkaline solution scc-Amino effect J Heterocyclic Chem 52 681-687. doi 10.1002/jhet2154... 

Antiproliferative evaluation of certain indolo[3,2]quinoline derivatives were reported by Lu et al. [29]. The introduction of a hydroxyl group at the anilino-moiety resulted in the enhancement of antiproliferative activity in which the activity decreased in an order ofpara-OH > meta-OH > ortho-OH. The Ce alkylamino-substituted indolo[3,2]quinoline derivatives, exhibited comparable antiproliferative activities against all tested cancer cells. 

The type of synthesis in which the two-atom fragment supplies C-5 + C-6 is uncommon but useful in preparing pyrimidine- and 5,6,7,8-tetrahydroquinazoline-2,4-diamines. Thus, dicyandiamide (S78) with benzyl methyl ketone (S77) yields 6-methyl-5-phenylpyrimidine-2,4-diamine (S79), or with acetophenone it yields 6-phenylpyrimidine-2,4-diamine (62JOC2708). Likewise, with cyclohexanone it yields the tetrahydroquinazolinediamine (SSO) and by using N- substituted dicyandiamides, 2- and/or 4-alkylamino groups may be introduced (65JOC1837). 

Reaction of 2-[(benzotriazol-l-yl)alkylamino]pyridines 341 with open-chain electron-rich alkenes 342 in the presence of BF3-Et20 gave 4-substituted 1,2,3,4-tetrahydropyrido[l, 2-n]pyrimidinium tetrafluorobo-rates 343 (98S704). 

The addition of (Z)-3-(alkylamino)-2-butenoic acid esters to nitroalkenes derived from open-chain sugars gave a 50 50 mixture of diastereomeric products 32. The reaction of chiral 2-sub-stituted l-(2-nitroethenyl)pyrrolidines with zinc enolates of 3-substituted tetrahydro-2//-pyran-2-oncs in 1,2-dimethoxyethane at — 78 °C afforded the corresponding 3,3-disubstituted products in 82-96% ee via an addition-elimination process33. The stereochemical course of the reaction was determined by chemical correlation of (S)-( )-3-ethyltetrahydro-3-(2-ni-troethenyl)-2//-pyran-2-one with ( + )-quebrachamine. 

Rotational equilibria of 2-carbonyl substituted thiophene and furan derivatives were calculated and show that the 2-substituent favors the anti-isomer in thiophene <96MI199>. NMR shifts of 35 alkyl 3-hydroxythiophene-2-carboxylates and 3-alkylamino-l-(3-thienyloxy)-2-propanols have been compiled and analyzed <96HC17>. 

B. Reactions.—(/) Nucleophilic Attack at Phosphorus. A reinvestigation of the reaction between phosphorus trichloride and t-butylbenzene in the presence of aluminium chloride has shown that the product after hydrolysis is the substituted phosphinic acid (11), and not the expected phosphonic acid (12). Bis(A-alkylamino)phosphines have been reported to attack chlorodiphenyl phosphine with nitrogen, in the presence of a base, to give bis-(A-alkyl-A-diphenylphosphinoamino)phenylphosphines (13). In (13), the terminal phosphorus atoms are more reactive than the central one towards sulphur and towards alkyl halides. 

Nielson125 reports the synthesis of 7-((V-aIkylamino)- and T-(N,N-di-alkylamino)-l,3,5-triazaadamantanes by reductive alkylation of 94, which is obtained from 91 by an improved hydrogenation procedure (rhodium-charcoal catalyst, 25.5 psi). Paper chromatography54 and the Kovats indices and relative elution volumes of 1,3,5-triazaadamantane derivatives are measured.55 7-Amino-l,3,5-triazaadamantane is used as a vulcanization accelerator.127 7-(N,N-Dialkylamino)-l,3,5-triazaadamantanes are utilized as a new class of high-density fuel (DIADAM).128 Some 7-substituted 1,3,5-triazaadamantanes have bacteriostatic and fungistatic activity.129 7-Bromo-,... 

Hydrolysis of amino-alkylamino-l,2,5-thiadiazole 1-oxides 55 with concentrated aqueous HC1 gave the amidines 56 (Equation 4) <2001JME1231>. The hydrolysis reactions of 2-alkyl-4-amino-2,3-dihydro-l, 2,5-thiadiazol-3-one 1,1-dioxides 57 in the range 24-73 °C in buffered aqueous solutions gave the corresponding 2-amino-2-[(iV-alkyl-substituted-sulfamoyl)imino]acetic acid salts 58 (Equation 5) <1998JP0489>. 

---