tert-butyl 3-bromopropylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】37752

【品名】tert-butyl 3-bromopropylcarbamate

【CA登记号】

【分子式】C₈H₁₆BrNO₂

【分子量】238.12458

【元素组成】C 40.35% H 6.77% Br 33.56% N 5.88% O 13.44%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

Diethyl diazomalonate (III) was prepared by reaction of diethyl malonate (I) with p-tosyl azide (II) in the presence of Et3N. Subsequent coupling of (II) with 4-hydroxytetrahydropyran (IV) using dirhodium tetraacetate as the catalyst afforded ether (V). Alkylation of (V) with 3-(tert-butoxycarbonylamino)propyl bromide (VI) yielded adduct (VII). Finally, hydrolysis of ester groups of (VII) employing LiOH furnished the title dicarboxylic acid lithium salt.

参考文献中间体

合成目标

【1】 Fiorentino, S.; Allegretti, M.; Mantovanini, M.; Clavenna, G.; Caselli, G.; Gandolfi, C.A. (Dompé Farmaceutici SpA); Geminal carboxylic acids and esters thereof pharmaceutical formulations containing them useful in the treatment of bone dysmetabolism. EP 0792878; US 5908863 .

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)	16829	Diethyl malonate	105-53-3	C₇H₁₂O₄	详情	详情
(II)	37748	4-methylbenzenesulfonyl azide	941-55-9	C₇H₇N₃O₂S	详情	详情
(III)	37749	diethyl 2-diazomalonate		C₇H₁₀N₂O₄	详情	详情
(IV)	37750	tetrahydro-2H-pyran-4-ol; 4-Hydroxytetrahydropyran	2081-44-9	C₅H₁₀O₂	详情	详情
(V)	37751	diethyl 2-(tetrahydro-2H-pyran-4-yloxy)malonate		C₁₂H₂₀O₆	详情	详情
(VI)	37752	tert-butyl 3-bromopropylcarbamate		C₈H₁₆BrNO₂	详情	详情
(VII)	37753	diethyl 2-[3-[(tert-butoxycarbonyl)amino]propyl]-2-(tetrahydro-2H-pyran-4-yloxy)malonate		C₂₀H₃₅NO₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Catalytic hydrogenation of tetrahydropyridine (I) produced piperidine (II). Alkylation of (II) with N-(3-bromopropyl)phthalimide (III) gave (IV). Subsequent hydrazinolysis of the phthalimido group of (IV) yielded amine (V). In a related procedure, piperidine (II) was alkylated with N-Boc-3-bromopropylamine (VI) to give (VII), which was deprotected with HCl in EtOAc to give the diamino precursor (V).

参考文献中间体

合成目标

【1】 Rittle, K.; et al.; Dihydropyrimidinone C-5 amides as potent and selective alpha1A receptor antagonists. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 90.
【2】 Selnick, H.G.; Barrow, J.C.; Nanterment, P.G.; et al.; In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha1A receptor antagonists for the treatment of benign prostatic hyperplasia. J Med Chem 2000, 43, 14, 2703.
【3】 Selnick, H.G.; Nantermet, P.G.; Barrow, J.C. (Merck & Co., Inc.); alpha1a Adrenergic receptor antagonists. WO 0006565 .

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)	23465	4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine	1978-59-2	C₁₁H₁₂FN	详情	详情
(II)	39299	4-(4-fluorophenyl)piperidine	37656-48-7	C₁₁H₁₄FN	详情	详情
(III)	15216	N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione	5460-29-7	C₁₁H₁₀BrNO₂	详情	详情
(IV)	39300	2-[3-[4-(4-fluorophenyl)-1-piperidinyl]propyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₃FN₂O₂	详情	详情
(V)	39302	3-[4-(4-fluorophenyl)-1-piperidinyl]propylamine; 3-[4-(4-fluorophenyl)-1-piperidinyl]-1-propanamine		C₁₄H₂₁FN₂	详情	详情
(VI)	37752	tert-butyl 3-bromopropylcarbamate		C₈H₁₆BrNO₂	详情	详情
(VII)	39301	tert-butyl 3-[4-(4-fluorophenyl)-1-piperidinyl]propylcarbamate		C₁₉H₂₉FN₂O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

Condensation of 2-pyridylacetonitrile (I) with N,N-bis-(2-chloroethyl)benzylamine (II) under phase-transfer conditions produced the pyridylpiperidine (III). The cyano group of (III) was hydrolyzed to carboxamide (IV) with concentrated sulfuric acid and then decarboxylated to (V) by treatment with methanolic HCl. Subsequent hydrogenolysis of the N-benzyl group of (V) afforded piperidine (VI). N-Boc-3-bromopropylamine (VIII) was prepared by treatment of 3-bromopropylamine (VII) with di-tert-butyl dicarbonate. Alkylation of piperidine (VI) with bromide (VIII) gave adduct (IX). The N-Boc protecting group of (IX) was then removed by treatment with trifluoroacetic acid to yield intermediate aine (X).

参考文献中间体

合成目标

【1】 Wong, W.C.; Lagu, B.; Nagarathnam, D.; Marzabadi, M.R.; Gluchowski, C. (Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. EP 1021185; JP 2000506904; WO 9742956 .
【2】 Lagu, B.; Nagarathnam, D.; Marzabadi, M.R.; Wong, W.C.; Gluchowski, C. (Synaptic Pharmaceutical Corp.); Dihydropyrimidines and uses thereof. WO 9851311 .

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)	36179	2-(2-pyridinyl)acetonitrile		C₇H₆N₂	详情	详情
(II)	23122	N-benzyl-2-chloro-N-(2-chloroethyl)-1-ethanamine; N-Benzylbis(2-chloroethyl)amine	10429-82-0	C₁₁H₁₅Cl₂N	详情	详情
(III)	48382	1-benzyl-4-(2-pyridinyl)-4-piperidinecarbonitrile		C₁₈H₁₉N₃	详情	详情
(IV)	48383	1-benzyl-4-(2-pyridinyl)-4-piperidinecarboxamide		C₁₈H₂₁N₃O	详情	详情
(V)	48384	1-benzyl-4-(2-pyridinyl)piperidine		C₁₇H₂₀N₂	详情	详情
(VI)	48385	2-(4-piperidinyl)pyridine		C₁₀H₁₄N₂	详情	详情
(VII)	25449	3-bromo-1-propanamine; 3-bromopropylamine	18370-81-5	C₃H₈BrN	详情	详情
(VIII)	37752	tert-butyl 3-bromopropylcarbamate		C₈H₁₆BrNO₂	详情	详情
(IX)	48386	tert-butyl 3-[4-(2-pyridinyl)-1-piperidinyl]propylcarbamate		C₁₈H₂₉N₃O₂	详情	详情
(X)	48387	3-[4-(2-pyridinyl)-1-piperidinyl]propylamine; 3-[4-(2-pyridinyl)-1-piperidinyl]-1-propanamine		C₁₃H₂₁N₃	详情	详情

Extended Information