1H-imidazole-5-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】41951

【品名】1H-imidazole-5-carbaldehyde

【CA登记号】3034-50-2

【分子式】C₄H₄N₂O

【分子量】96.08864

【元素组成】C 50% H 4.2% N 29.15% O 16.65%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

Condensation of 3-nitrobenzenesulfonyl chloride (I) with tetrahydroquinoline (II) in the presence of pyridine gave sulfonamide (III). Reduction of the nitro group of (III) with stannous chloride produced the aniline derivative (IV). The title compound was then obtained by reductive alkylation of amine (IV) with 4-formylimidazole (V) using sodium triacetoxyborohydride as the reducing reagent.

参考文献中间体

合成目标

【1】 Hunt, J.T.; Manne, V.; Ding, C.Z.; Ricca, C.; 3-Imidazolylmethylaminophenylsulfonyltetrahydroquinolines, a novel series of farnesyltransferase inhibitors. Bioorg Med Chem Lett 2000, 10, 3, 273.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	41948	3-nitrobenzenesulfonyl chloride	121-51-7	C₆H₄ClNO₄S	详情	详情
(II)	23859	1,2,3,4-tetrahydroquinoline	635-46-1	C₉H₁₁N	详情	详情
(III)	41949	1-[(3-nitrophenyl)sulfonyl]-1,2,3,4-tetrahydroquinoline		C₁₅H₁₄N₂O₄S	详情	详情
(IV)	41950	3-[3,4-dihydro-1(2H)-quinolinylsulfonyl]phenylamine; 3-[3,4-dihydro-1(2H)-quinolinylsulfonyl]aniline		C₁₅H₁₆N₂O₂S	详情	详情
(V)	41951	1H-imidazole-5-carbaldehyde	3034-50-2	C₄H₄N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The cyclization between 5-bromoisatoic anhydride (I) and D-phenylalanine methyl ester (II) in the presence of DMAP in refluxing pyridine produced the benzodiazepindione (III), which was further reduced to the benzodiazepine (IV) by treatment with borane in THF. Displacement of the bromide group of (IV) with cuprous cyanide in hot N-methylpyrrolidone furnished nitrile (V). Acylation of the aliphatic nitrogen of (V) with 2-thienylsulfonyl chloride (VI) gave rise to sulfonamide (VII). Finally, the title compound was obtained by reductive alkylation of (VII) with 4-formylimidazole (VIII) by means of either treatment with sodium triacetoxyborohydride or, in an improved procedure, using triethylsilane in the presence of trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Chen, B.C.; et al.; Novel triethylsilane mediated reductive N-alkylation of amines: Improved synthesis of 1-(4-imidazolyl)methyl-4-sulfonylbenzodiazepines new farnesyltransferase inhibitors. Tetrahedron Lett 2001, 42, 7, 1245.
【3】 Ding, C.Z.; Hunt, J.T.; Kim, S.-H.; Mitt, T.; Bhide, R.; Leftheris, K. (Bristol-Myers Squibb Co.); Inhibitors of farnesyl protein transferase. EP 0892797; JP 2000502356; US 6011029; WO 9730992 .
【2】 Batorsky, R.; Hunt, J.T.; Ding, C.Z.; et al.; Discovery of (R)-7-cyano-2,3,4,5-tetrahydro-1-(1-H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J Med Chem 2000, 43, 20, 3557.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	47112	6-bromo-2H-3,1-benzoxazine-2,4(1H)-dione		C₈H₄BrNO₃	详情	详情
(II)	12324	methyl (2R)-2-amino-3-phenylpropanoate	21685-51-8	C₁₀H₁₃NO₂	详情	详情
(III)	47113	(3R)-3-benzyl-7-bromo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione		C₁₆H₁₃BrN₂O₂	详情	详情
(IV)	47114	(3R)-3-benzyl-7-bromo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine		C₁₆H₁₇BrN₂	详情	详情
(V)	47115	(3R)-3-benzyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carbonitrile		C₁₇H₁₇N₃	详情	详情
(VI)	40760	2-thiophenesulfonyl chloride	16629-19-9	C₄H₃ClO₂S₂	详情	详情
(VII)	47116	(3R)-3-benzyl-4-(2-thienylsulfonyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carbonitrile		C₂₁H₁₉N₃O₂S₂	详情	详情
(VIII)	41951	1H-imidazole-5-carbaldehyde	3034-50-2	C₄H₄N₂O	详情	详情

Extended Information