241483-00-1Relevant articles and documents
An improved process for the synthesis of DMTMM-based coupling reagents
Raw, Steven A.
, p. 946 - 948 (2009)
A simple, robust and high-yielding process for the preparation of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate (DMTMM BF4) and hexafluorophosphate (DMTMM PF6) has been developed, which avoids the use of expensive or unusual reagents.
Pd-PEPPSI-IPentAn Promoted Deactivated Amination of Aryl Chlorides with Amines under Aerobic Conditions
Huang, Fei-Dong,Xu, Chang,Lu, Dong-Dong,Shen, Dong-Sheng,Li, Tian,Liu, Feng-Shou
, p. 9144 - 9155 (2018/07/21)
We report herein a highly efficient Pd-catalyzed amination by "bulky-yet-flexible" Pd-PEPPSI-IPentAn complexes. The relationship between the N-heterocyclic carbenes (NHCs) structure and catalytic properties was discussed. Sterically hindered (hetero)aryl chlorides and a variety of aliphatic and aromatic amines can be applied in this cross-coupling, which smoothly proceeded to provide desired products. The operationally simple protocol highlights the rapid access to CAr-N bond formation under mild conditions without the exclusion of air and moisture.
An Efficient Synthesis of Pemetrexed Disodium
Qi,Wen,Li,Bai,Chen,Wang
, p. 1565 - 1569 (2015/10/06)
An efficient synthetic method for the pemetrexed disodium has been developed using methyl 4-iodobenzoate and 3-buten-1-ol as starting materials via six steps. The developed process avoided some tedious workup procedures and unfriendly reagents compared with the reported synthetic routes. In addition, two impurities generated in the process were isolated and characterized by 1H NMR, 13C NMR, and HRMS. The mechanisms of the two impurities were also discussed, and the impurities could be easily removed by suitable workup procedures. The overall yield of pemetrexed disodium was increased from 12.8% (literature) to 34.9%. Therefore, this cost-effective, environmental friendly, and high-yielding process is more suitable for scale-up production of pemetrexed disodium.
Study on 1,3,5-triazine chemistry in dehydrocondensation: Gauche effect on the generation of active triazinylammonium species
Kunishima, Munetaka,Ujigawa, Takae,Nagaoka, Yoshie,Kawachi, Chiho,Hioki, Kazuhito,Shiro, Motoo
, p. 15856 - 15867 (2013/01/16)
The reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with various nitrogen-containing compounds, particularly tertiary amines (tert-amines), has been studied for the preparation of 2-(4,6-dimethoxy-1,3,5-triazinyl) trialkylammonium salts [DMT-Am(s)]. DMT-Ams derived from aliphatic tert-amines exhibited activity for the dehydrocondensation between a carboxylic acid and an amine to form an amide in a model reaction. Based on a conformational analysis of DMT-Ams and tert-amines by NMR and X-ray diffraction methods, we concluded that a β-alkyl group maintained in a gauche relationship with the nitrogen lone pair of tert-amines significantly hinders the approach of CDMT to the nitrogen. Thus, trimethylamine and quinuclidine without such alkyl groups readily react with CDMT whereas triethylamine, possessing two or three such gauche β-alkyl groups in the stable conformations, does not react at all. The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of DMT-Ams possessing various tertiary amine moieties. An investigation of the dehydrocondensation activity of tert-amines in a CDMT/tert-amine system that involves in situ generation of DMT-Am, showed that the gauche effect of the β-alkyl group becomes quite pronounced; the yield of the amide decreases significantly with tert-amines possessing an unavoidable gauche β-alkyl group. Thus, the tert-amine/CDMT systems are useful for judging whether tert-amines can readily react with CDMT without isolation of DMT-Ams. The right approach! The structure-activity relationship of nitrogen-containing compounds including aliphatic tertiary amines in the reaction with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) has been investigated (see scheme). The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of triazine-based dehydrocondensation reagents (DMT-Ams) possessing various tertiary amine moieties. Copyright
Transformation of tertiary amines into alkylating reagents by treatment with 2-chloro-4,6-dimethoxy-1,3,5-triazine. A synthetic application of side-reaction accompanying coupling by means of 4-(4,6-dimethoxy-[1,3,5] triazin-2-yl)-4-methyl-morpholin-4-ium chloride (DMTMM)
Kolesinska,Kaminski
experimental part, p. 2115 - 2123 (2009/04/07)
Mild reaction conditions are described for the preparation of a number of alkyl chlorides and 2-dialkyl(aryl)amino-4,6-dirnethoxy-1,3,5-triazines by dealkylation of quaternary triazinylammonium chlorides formed as reactive intermediates in reaction of tertiary amines with 2-chloro-4,6-dimethoxy-1,3,5- triazine. The high selectivity of substitution was observed within the reactivity order of the alkyl groups: benzyl ～ allyl > methyl > n-alkyl. Studies on dealkylation of S-(-)-J-dimethyl-(1-phenylethyl)amine to R-(+)-1-chloro-1-phenylethane revealed that reaction proceeded with an inversion of configuration on the carbon atom as may be expected for SN2 type substitution. The scope of reaction was extended by exchange of anion in quaternary triazinylammonium chlorides with 1-, SCN-, C6H5O-, CH3COO- followed by N-dealkylation step.
METHODS AND COMPOUNDS PRODUCING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREOF
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Page 73, (2008/06/13)
Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided
4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride: An efficient condensing agent leading to the formation of amides and esters
Kunishima, Munetaka,Kawachi, Chiho,Morita, Jun,Terao, Keiji,Iwasaki, Fumiaki,Tani, Shohei
, p. 13159 - 13170 (2007/10/03)
4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N- methylmorpholine (NMM) in THF, and characterized. Condensation of carboxylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yields. The corresponding esters can be obtained by esterification of carboxylic acids with DMTMM in methanol, ethanol, isopropyl alcohol, or t-butyl alcohol in the presence of NMM. The amount of alcohols can be reduced to a stoichiometric amount by conducting the reaction in THF. Since the reactions proceed under atmospheric conditions without drying of the solvent, and the co- product (4,6-dimethoxy-1,3,5-triazin-2(1H)-one) arising from DMTMM after condensation can be readily removed by extraction, this method is a very practical one.
Synthesis and characterization of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)- 4-methylmorpholinium chloride
Kunishima, Munetaka,Kawachi, Chiho,Iwasaki, Fumiaki,Terao, Keiji,Tani, Shohei
, p. 5327 - 5330 (2007/10/03)
4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6- dimethoxy-1,3,5-triazine and N-methylmorpholine in THF, and fully characterized. Condensation of carboxylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yield.
Concerted displacement mechanism at trigonal carbon: the aminolysis of 4-aryloxy-2,6-dimethoxy-1,3,5-triazines
Shakes, Janice,Raymond, Christel,Rettura, Donatella,Williams, Andrew
, p. 1553 - 1558 (2007/10/03)
4-Aryloxy-1,3,5-triazines undergo bimolecular nucleophilic displacement reactions with amines and pyridines to yield the 4-substituted triazine and aryloxide ion.Rate constants in aqueous solution for the bimolecular reaction of morpholine and 4-dimethylaminopyridine with the title ethers obey the Hammett ? evaluation with Hammett ρlg values 1.65 and 0.82, respectively.Comparison of the ρlg values with the Hammett ρeq for the equilibrium constants indicates that build-up of effective charge on the departing ether oxygen in the transition structures is less than half of that for complete bond fission.Rate constants for the reaction of substituted pyridines with the 4-nitro- and 3,4-dinitro-phenyl ethers obey Broensted equations with exponents βnuc of 0.68 and 1.06, respectively.The build-up of effective charge in bond formation is greater than half of that expected for complete bond formation.Variation in βnuc and ρlg as a function of leaving group and nucleophile structure, respectively, is consistent with substantial coupling between bond forming and bond breaking.The ratio of the Leffler exponents in the pyridinolysis reactions, αnuc/αlg, is greater than unity, consistent with an imbalance between bond fission and bond formation and indicating an accumulation of negative charge in the heteroaromatic nucleus in the transition structure 29percent of that expected for adduct formation.
