Method for preparing pyridine intermediateThis invention relates to a method for preparing a pyridine intermediate, and particularly relates to a method of preparing substituted pyridine by using ammonium carbamate as a nitrogen source to prepare enamine as an intermediate compound, and thereafter reacting the intermediate compound with other compounds again. According to the method, the substituted pyridine can be prepared with a high yield in a short reaction time by the method consisting of at least two steps. In addition, the method is performed under solvent-free and catalyst-free conditions, and therefore the method exhibits a highly efficient arrangement effect. Accordingly, the method can be used widely in the fields of medicine or pharmaceuticals, in fields where the substituted pyridine is prepared.Manufacture has the method for compound of structure for chemical formula 4, and the method includes:step (a), makes the compound with the structure of chemical formula 1 react with aminoquinoxaline, system make the enamine intermediates compound of the structure with chemical formula 2；andstep (b), makes the intermediate with the structure of chemical formula 2 and the structure with chemical formula 3 compound reaction, manufacture the compound of structure with chemical formula 4,described r1for hydrogen；c1-c6alkyl；hydroxyl c1-c6alkyl；c1-c6haloalkyl；c2-c6 thiazolinyl；c2-c6haloalkenyl group；by c1-c2alkoxy carbonyl or the substituted vinyl of phenyl；c2-c6 alkynyl；c2-c6halo alkynyl；by tms, hydroxyl, c1-c2alkoxyl, c1-c2 alkoxy carbonyl or the substituted acetenyl of phenyl；c3-c6allene base；c3-c6cycloalkyl；by halogen the substituted c of element3-c6cycloalkyl；c1-c6alkoxyl；c3-c6alkenyloxy group；c3-c6alkynyloxy group； c1-c6halogenated alkoxy；c3-c6haloalkene epoxide；cyano group-c1-c4alkoxyl；c1-c4alcoxyl base-c1-c4alkoxyl；c1-c4alkylthio group-c1-c4alkoxyl；c1-c4alkyl sulphinyl-c1-c4 alkoxyl；c1-c4alkyl sulphonyl-c1-c4alkoxyl；c1-c4alkoxy carbonyl-c1-c4alcoxyl base；c1-6alkylthio group；c1-c6alkyl sulphinyl；c1-c6alkyl sulphonyl；c1-c6halo alkylthio group；c1-c6alkylsulfinyl；c1-c6halogenated alkyl sulfonyl；c1-c4alcoxyl base carbonyl-c1-c4alkylthio group；c1-c4alkoxy carbonyl-c1-c4alkyl sulphinyl；c1-c4alkane epoxide carbonyl-c1-c4alkyl sulphonyl；benzyl-s (o)n1-；c1-c6alkyl amino；c2-c6 dialkyl amido；c1-c6alkyl amino sulfonyl；two-(c1-c6alkyl amino) sulfonyl； benzyloxy；benzyl；phenyl；phenoxy group；thiophenyl；phenylsufinyl；phenyl sulfonyl； by c1-c3alkyl, c1-c3haloalkyl, c1-c3alkoxyl, c1-c3halogenated alkoxy, halogen element, cyano group or the substituted group containing phenyl of nitro；os(o)n2-r21；n(r23)-s (o)n3-r22；cyano group；carbamoyl；c1-c4alkoxy carbonyl；formoxyl；halogen； thiocyanogen；amino；c1-c4alkoxy-c1-c4alkyl；c1-c4alkyl-s (o)n4-c1-c4 alkyl；cyano group-c1-c4alkyl；c1-c6alkyl carbonyl oxy-c1-c4alkyl；c1-c4alkoxyl carbonyl base-c1-c4alkyl；c1-c4alkoxyl carbonyloxy group-c1-c4alkyl；c1-c4thiocyanogen-c1-c4alkane base；benzoyloxy-c1-c4alkyl；c2-c6oxyranyle；c1-c4alkyl amino-c1-c4 alkyl；two-(c1-c4-alkyl) amino-c1-c4alkyl；c1-c12alkylthiocarbonyl-c1-c4alkane base；formoxyl-c1-c4alkyl；5-to 10-unit monocycle or fused bicyclic ring system, as described ring system, can be aromatic ring or fractional saturation ring, can comprise 1 to 4 be selected from nitrogen, oxygen and hetero atom in sulfur, can pass through c1-c4alkylidene ,-ch=ch-,-c ≡ c-,-ch2o-、 -ch2n(c1-c4alkyl)-,-ch2so-or-ch2so2-base is combined with pyridine ring, each ring system oxygen atom and the sulphur atom of less than 2 can be comprised, for from by c1-c6alkyl, c1-c6halo alkyl, c3-c6thiazolinyl, c3-c6haloalkenyl group, c3-c6alkynyl, c3-c6halo alkynyl, c1-c6 alkoxyl, c1-c6halogenated alkoxy, c3-c6alkenyloxy group, c3-c6alkynyloxy group, sulfydryl, c1-c6 alkylthio group, c1-c6halogenated alkylthio, c3-c6alkenylthio group, c3-c6haloalkene sulfenyl, c3-c6 alkynes sulfenyl, c2-c5alkoxyl alkylthio group, c3-c5acetyl group alkylthio group, c3-c6alkoxy carbonyl alkylthio group, c2-c4cyano group alkylthio group, c1-c6alkyl sulphinyl, c1-c6haloalkyl asia sulphur acyl group, c1-c6alkyl sulphonyl, c1-c6halogenated alkyl sulfonyl, amino-sulfonyl, c1-c2 alkyl amino sulfonyl, two-(c1-c2alkyl) amino-sulfonyl, two-(c1-c4alkyl) ammonia substituted monosubstituted, two replacements of base, halogen, cyano group, nitro, phenyl and benzylthio or three replacements the one selected in type ring system；described r2for c1-6haloalkyl；described r3for hydrogen or c1-c6alkyl.
메틸 2-프로필-6-(트리플루오로메틸) 니코티네이트의 제조방법본 명세서는 암모니움 카바메이트를 질소 소스로 사용하여 엔아민을 중간체 화합물로 제조하고, 이를 다시 다른 화합물과 반응시켜 치환된 피리딘을 제조하는 방법에 관한 것이다. 본 명세서의 방법에 따르면 적어도 2단계로 이루어진 방법에 의하여 높은 수율과 짧은 반응 시간에 치환된 피리딘을 제조할 수 있다. 또한 이러한 방법에 따르면 무용매 및 무촉매 조건 하에서 반응을 진행하는 것이므로 배치 효율이 매우 높은 효과를 나타낸다. 그러므로, 의약 또는 약학 분야에 있어서, 치환된 피리딘을 제조하는 분야에서 널리 사용될 수 있다. 화학식 4의 구조를 가지는 화합물을 제조하는 방법으로서,(a) 화학식 1의 구조를 가지는 화합물과 암모니움 카바메이트를 반응시켜 화학식 2의 구조를 가지는 엔아민(enamine) 중간체 화합물을 제조하는 단계;(b) 화학식 2의 구조를 가지는 중간체와 화학식 3의 구조를 가지는 화합물을 반응시켜 화학식 4의 구조를 가지는 화합물을 제조하는 단계;를 포함하는 방법.[화학식 1][이미지][화학식 2][이미지][화학식 3][이미지][화학식 4][이미지]상기 R1은 수소; C1-C6알킬; 하이드록시 C1-C6알킬; C1-C6할로알킬; C2-C6알켄일; C2-C6할로알켄일; C1-C2알콕시카르보닐 또는 페닐로 치환된 비닐; C2-C6알킨일; C2-C6할로알킨일; 트리메틸실릴,하이드록실, C1-C2알콕시, C1-C2알콕시카르보닐 또는 페닐로 치환된 에티닐; C3-C6알렌일(allenyl); C3-C6사이클로알킬; 할로겐으로 치환된 C3-C6사이클로알킬; C1-C6알콕시; C3-C6알켄일옥시; C3-C6알킨일옥시; C1-C6할로알콕시; C3-C6할로알켄일옥시; 시아노-C1-C4알콕시; C1-C4알콕시-C1-C4알콕시; C1-C4알킬티오-C1-C4알콕시; C1-C4알킬설피닐-C1-C4알콕시; C1-C4알킬설포닐-C1-C4알콕시; C1-C4알콕시카르보닐-C1-C4알콕시; C1-6알킬티오; C1-C6알킬설피닐; C1-C6알킬설포닐; C1-C6할로알킬티오; C1-C6할로알킬설피닐; C1-C6할로알킬설포닐; C1-C4알콕시카르보닐- C1-C4알킬티오; C1-C4알콕시카르보닐-C1-C4알킬설피닐; C1-C4알콕시카르보닐-C1-C4알킬설포닐; 벤질-S(O)n1-; C1-C6알킬아미노; C2-C6디알킬아미노; C1-C6알킬아미노설포닐; 디-(C1-C6알킬아미노)설포닐; 벤질옥시; 벤질; 페닐; 페녹시; 페닐티오; 페닐설피닐; 페닐설포닐; 및 C1-C3알킬, C1-C3할로알킬, C1-C3알콕시, C1-C3할로알콕시, 할로겐, 시아노 또는 니트로로 치환된 페닐함유기(pheynyl-containing groups); OS(O)n2-R21; N(R23)-S(O)n3-R22; 시아노; 카르바모일; C1-C4알콕시카르보닐; 포르밀; 할로겐; 티오시아나토; 아미노; C1-C4알콕시-C1-C4알킬; C1-C4알킬-S(O)n4-C1-C4알킬; 시아노-C1-C4알킬; C1-C6알킬카르보닐옥시-C1-C4알킬; C1-C4알콕시카르보닐-C1-C4 알킬; C1-C4알콕시카르보닐옥시-C1-C4알킬; C1-C4티오시아나토-C1-C4알킬; 벤조일옥시-C1-C4알킬; C2-C6옥시란일(oxiranyl); C1-C4알킬아미노-C1-C4알킬; 디-(C1-C4-알킬)아미노-C1-C4알킬; C1-C12알킬티오카르보닐-C1-C4알킬; 포르밀-C1-C4알킬; 5- 내지 10-원자 모노사이클릭 또는 융합 바이사이클릭 고리 시스템으로서, 방향족 또는 부분적으로 포화된 것일 수 있고, 질소, 산소, 및 황으로 구성된 군으로부터 선택된 헤테로 원자를 1개 내지 4개 포함할 수 있고, C1-C4알킬렌, -CH=CH-, -C≡C-, -CH2O-, -CH2N(C1-C4알킬)-, -CH2SO-, 또는 -CH2SO2-기를 통하여 피리딘 고리에 결합될 수 있으며, 각 고리 시스템이 2개 이하의 산소 원자 및 황 원자를 포함할 수 있고, C1-C6알킬, C1-C6할로알킬, C3-C6알켄일, C3-C6할로알켄일, C3-C6알킨일, C3-C6할로알킨일, C1-C6알콕시, C1-C6할로알콕시, C3-C6알켄일옥시, C3-C6알킨일옥시, 머캅토, C1-C6알킬티오, C1-C6할로알킬티오, C3-C6알켄일티오, C3-C6할로알켄일티오, C3-C6알킨일티오, C2-C5알콕시알킬티오, C3-C5아세틸알킬티오, C3-C6알콕시카르보닐알킬티오, C2-C4cyano알킬티오, C1-C6알킬설피닐, C1-C6할로알킬설피닐, C1-C6알킬설포닐, C1-C6할로알킬설포닐, 아미노설포닐, C1-C2알킬아미노설포닐, 디-(C1-C2알킬)아미노설포닐, 디-(C1-C4알킬)아미노, 할로겐, 시아노, 니트로, 페닐 및 벤질티오로 치환된 모노-, 디- 또는 트리 치환형 고리 시스템으로 구성된 군으로부터 선택된 하나이며;상기 R2는 C1-6 할로 알킬이며;상기 R3는 수소 또는 C1-C6알킬임.