- Microwave-assisted α-halogenation of 2-methylquinolines with tetrabutylammonium iodide and 1,2-dichloroethane (1,2-dibromoethane)
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A simple and efficient methodology permitting the halogenation of 2-methylquinolines into 2-(chloromethyl)quinolines or 2-(bromomethyl)quinolines in the tetrabutylammonium iodide and 1,2-dichloroethane (1,2-dibromoethane) system has been developed for the first time. The halogenation can be rapidly completed with good to excellent yields and high selectivity under microwave irradiation.
- Xie, Yuanyuan,Li, Lehuan
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supporting information
p. 3892 - 3895
(2014/07/08)
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- The process development of RG 12525 (2-{[4-(Tetrazol-5-ylmethylphenyl)-methoxy]phenoxymethyl}quinoline)
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This contribution describes process improvements to provide a practical and cost-effective synthesis for the manufacture of RG 12525 which resulted in a 3-fold increase in overall yield. Improved solvent systems for chlorination and azidation reactions are described. Adjustments to the tetrazole-forming step eliminated azide sublimation and minimised this risk on scale-up. A robust solvent system was found to control the polymorphic form during crystallisation, which had hitherto been difficult due to the near-equivalence of melting points (154 and 157 °C) of the two known forms.
- Bridge, Andrew W.,Jones, Ronald H.,Kabir, Humayun,Kee, Alex A.,Lythgoe, David J.,Nakach, Mustafa,Pemberton, Clive,Wrightman, John A.
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- Efficient pyridinylmethyl functionalization: Synthesis of 10,10-bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (DMP 543), an acetylcholine release enhancing agent
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2-Fluoro-4-methylpyridine (3) is efficiently functionalized by chlorination, hydrolysis and methane-sulfonylation into the novel alkylating agent 7. This mesylate is used for the bisalkylation of anthrone under carefully defined conditions to prepare the cognition enhancer drug candidate 1. This process proceeds in up to 37% overall yield and is adaptable for large scale synthesis.
- Pesti,Huhn,Yin,Xing,Fortunak,Earl
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p. 7718 - 7722
(2007/10/03)
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- Side chain chlorination process of heterocycles
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A novel method of chlorinating the alkyl side chains of a nitrogen containing heterocyclic comprising reacting an alkyl substituted heterocycle with trichloroisocyanuric acid at temperatures of 20° to 200° C. to obtain the same in high yields.
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- Side Chain Chlorinations of N-Heterocyclic Compounds by Trichloroisocyanuric Acid (TCC)
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N-Heterocyclic compounds such as 2-methylpyridines, 2-methylquinoline, and 2-methylquinoxaline react with trichloroisocyanuric acid (TCC) without the addition of an initiator to provide the corresponding chloromethyl derivatives in good yields.
- Jeromin, Guenter E.,Orth, Winfried,Rapp, Bernd,Weiss, Wolfgang
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p. 649 - 652
(2007/10/02)
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- Studies on Ketene and Its Derivatives. CXIII. Reaction of Dichloroketene with Aromatic Amine N-Oxides
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Reaction of dichloroketene with pyridine 1-oxide (1) gave four products, namely, 2-dichloromethylpyridine (2), 4-dichloromethylpyridine (3), 3,3,7-trichloro-6-dichloroacetyl-2-oxo-2,3,3a,6,7,7a-hexahydrofuropyridine (4), and 3,3-dichloro-6-dichloroacetyl-7-hydroxy-2-oxo-2,3,3a,6,7,7a-hexahydrofuropyridine (5).Reaction of dichloroketene with 1, followed by treatment with abs. methanol gave 3, methyl 2,2-dichloro-2-(2-pyridyl)acetate (6), and methyl 2,2-dichloro-2-(4-pyridyl)acetate (7).Similar reaction of dichloroketene with methylpyridine 1-oxides gave the corresponding 2-dichloro and 4-dichloro methylpyridines.On the other hand, reaction of dichloroketene with 2,6-dimethylpyridine 1-oxide (18), followed by treatment with abs. methanol gave 4-dichloromethyl-2,6-dimethylpyridine (19) and bis(2,6-dimethyl-4-pyridyl)dichloromethane (21).Dichloroketene also reacted with quinoline 1-oxide (24) and isoquinoline 2-oxide (29) to give the corresponding dichloromethyl derivatives (25 and 26, and 30, respectively).Keywords --- aromatic amine N-oxide; dichloroketene; dichloromethylpyridine; dichloromethylquinoline; dichloromethylisoquinoline
- Katagiri, Nobuya,Niwa, Ryuji,Furuya, Yoichi,Kato, Tetsuzo
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p. 1833 - 1841
(2007/10/02)
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