6-phenyl-1-(1-piperazinyl)-1-hexanone -Drug Synthesis Database

【结构式】

【分子编号】51127

【品名】6-phenyl-1-(1-piperazinyl)-1-hexanone

【CA登记号】

【分子式】C₁₆H₂₄N₂O

【分子量】260.37944

【元素组成】C 73.81% H 9.29% N 10.76% O 6.14%

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：(XII)

Coupling of 6-phenylhexanoic acid (X) with N-Boc-piperazine (IX) to give (XI), followed by acid deprotection of the Boc group of (XI), provided (6-phenylhexanoyl)piperazine (XII). This was converted to the carbamoyl chloride (XIII) upon treatment with phosgene. The condensation of carbamoyl chloride (XIII) with azetidinone (VIII) gave rise to the urea derivative (XIV). After acid cleavage of the Boc protecting group of (XIV), the resulting piperidine (XV) was condensed with N,N'-dicarbobenzoxy-S-methylisothiourea (XVI) in the presence of HgCl2, yielding the protected guanidine (XVII). This was finally deprotected by catalytic hydrogenolysis over Pd/C.

参考文献中间体

合成目标

【1】 Treuner, U.; Kronenthal, D.R.; Xu, Z.; Seiler, S.; Slusarchyk, W.A.; Bisacchi, G.; Randazzo, M.E.; Sutton, J.C.; Shi, Z.; Zahler, R.; Schwinden, M.D. (Bristol-Myers Squibb Co.); Amidino and guanidino azetidinone tryptase inhibitors. WO 9967215 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	51123	tert-butyl 3-([(2S,3R)-2-[(benzyloxy)carbonyl]-4-oxoazetidinyl]methyl)-1-piperidinecarboxylate		C₂₂H₃₀N₂O₅	详情	详情
(IX)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(X)	51125	6-Phenylcaproic acid; 6-Phenylhexanoic acid; Benzenehexanoic acid	5581-75-9	C₁₂H₁₆O₂	详情	详情
(XI)	51126	tert-butyl 4-(6-phenylhexanoyl)-1-piperazinecarboxylate		C₂₁H₃₂N₂O₃	详情	详情
(XII)	51127	6-phenyl-1-(1-piperazinyl)-1-hexanone		C₁₆H₂₄N₂O	详情	详情
(XIII)	51128	4-(6-phenylhexanoyl)-1-piperazinecarbonyl chloride		C₁₇H₂₃ClN₂O₂	详情	详情
(XIV)	51129	tert-butyl 3-[((2S,3R)-2-[(benzyloxy)carbonyl]-4-oxo-1-[[4-(6-phenylhexanoyl)-1-piperazinyl]carbonyl]azetidinyl)methyl]-1-piperidinecarboxylate		C₃₉H₅₂N₄O₇	详情	详情
(XV)	51130	benzyl (2S,3R)-4-oxo-1-[[4-(6-phenylhexanoyl)-1-piperazinyl]carbonyl]-3-(3-piperidinylmethyl)-2-azetidinecarboxylate		C₃₄H₄₄N₄O₅	详情	详情
(XVI)	32861	benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate		C₁₈H₁₈N₂O₄S	详情	详情
(XVII)	51131	benzyl (2S,3R)-3-[[1-([[(benzyloxy)carbonyl]amino][[(benzyloxy)carbonyl]imino]methyl)-3-piperidinyl]methyl]-4-oxo-1-[[4-(6-phenylhexanoyl)-1-piperazinyl]carbonyl]-2-azetidinecarboxylate		C₅₁H₅₈N₆O₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Alkaline hydrolysis of ester (I), followed by chlorination of the resulting carboxylic acid (II) by means of oxalyl chloride furnishes the acid chloride (III). This is then treated with morpholine (IV) to provide the corresponding amide (V). Displacement of the bromide group of (V) with 3-(aminomethyl)pyridine (VI) leads to the secondary amine (VII), which is further protected as the N-Boc derivative (VIII) employing di-tert-butyl dicarbonate. Addition of the 2-lithiated benzimidazole (IX) to the morpholine amide (VIII) gives rise to ketone (X). The N-Boc group of (X) is finally cleaved by treatment with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Kawasaki, K.; Masubuchi, M.; Morikami, K.; Sogabe, S.; Aoyama, T.; Ebiike, H.; Niizuma, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki,Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3. Bioorg Med Chem Lett 2003, 13, 1, 87.

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)	51127	6-phenyl-1-(1-piperazinyl)-1-hexanone		C₁₆H₂₄N₂O	详情	详情
(II)	63703	4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-carboxylic acid		C₁₃H₁₃BrO₄	详情	详情
(III)	63704	4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-carbonyl chloride		C₁₃H₁₂BrClO₃	详情	详情
(IV)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(V)	63705	{4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-yl}(4-morpholinyl)methanone		C₁₇H₂₀BrNO₄	详情	详情
(VI)	18731	3-pyridinylmethanamine; 3-pyridinylmethylamine	3731-52-0	C₆H₈N₂	详情	详情
(VII)	63706	[3-methyl-4-({3-[(3-pyridinylmethyl)amino]propyl}oxy)-1-benzofuran-2-yl](4-morpholinyl)methanone		C₂₃H₂₇N₃O₄	详情	详情
(VIII)	63707	1,1-dimethylethyl 3-{[3-methyl-2-(4-morpholinylcarbonyl)-1-benzofuran-4-yl]oxy}propyl(3-pyridinylmethyl)carbamate		C₂₈H₃₅N₃O₆	详情	详情
(IX)	63708	[1-(2-propenyl)-1H-benzimidazol-2-yl]lithium		C₁₀H₉LiN₂	详情	详情
(X)	63709	1,1-dimethylethyl 3-[(3-methyl-2-{[1-(2-propenyl)-1H-benzimidazol-2-yl]carbonyl}-1-benzofuran-4-yl)oxy]propyl(3-pyridinylmethyl)carbamate		C₃₄H₃₆N₄O₅	详情	详情

Extended Information