(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine -Drug Synthesis Database

【结构式】

【分子编号】53631

【品名】(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine

【CA登记号】n/a

【分子式】C₁₁H₁₅NO₂

【分子量】193.24564

【元素组成】C 68.37% H 7.82% N 7.25% O 16.56%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(XVII)

The required (S)-alpha-propylpiperonyl alcohol (XV) was prepared by two alternative routes. Asymmetric addition of di-n-propyl zinc to piperonal (X) in the presence of titanium isopropoxide and the chiral bis-triflamide (XI) yielded the (S)-alcohol (XV) in high enantiomeric excess. Alternatively, ketone (XIII) was reduced with the oxazaborolidine-borane complex (XIV) to give (XV). Treatment of the (S)-alcohol (XV) with DPPA in the presence of DBU produced the (R)-azide (XVI). This was then reduced with LiAlH4 to yield amine (XVII) with some loss of optical purity. Optical enrichment was achieved by crystallization as the D-pyroglutamic acid salt. The (R)-amine (XVII) was converted to isocyanate (XVIII) by treatment with phosgene. Finally, coupling between isocyanate (XVIII) and azetidinone (IX) in the presence of DBU in acetonitrile led to the title compound.

参考文献中间体

合成目标

【1】 Cvetovich, R.J.; et al.; An asymmetric synthesis of L-694,458, a human leukocyte elastase inhibitor, via novel enzyme resolution of beta-lactam esters. J Org Chem 1996, 61, 19, 6575.
【2】 Amato, J.S.; Cvetovich, R.; Hartner, F.W. (Merck & Co., Inc.); Process for preparing substd. azetidinones. WO 9716448 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	53626	(4S)-3,3-diethyl-4-{4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy}-2-azetidinone	n/a	C₁₉H₂₇N₃O₃	详情	详情
(X)	10127	1,3-Benzodioxole-5-carbaldehyde; Heliotropine	120-57-0	C₈H₆O₃	详情	详情
(XI)	53627	trifluoro-N-((1R,2R)-2-{[(trifluoromethyl)sulfonyl]amino}cyclohexyl)methanesulfonamide	n/a	C₈H₁₂F₆N₂O₄S₂	详情	详情
(XIII)	53629	1-(1,3-benzodioxol-5-yl)-1-butanone	63740-97-6	C₁₁H₁₂O₃	详情	详情
(XIV)	20631	(R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole	112022-83-0	C₁₈H₂₀BNO	详情	详情
(XV)	53628	(1S)-1-(1,3-benzodioxol-5-yl)-1-butanol	n/a	C₁₁H₁₄O₃	详情	详情
(XVI)	53630	(1R)-1-(1,3-benzodioxol-5-yl)butyl azide; 5-[(1R)-1-azidobutyl]-1,3-benzodioxole	n/a	C₁₁H₁₃N₃O₂	详情	详情
(XVII)	53631	(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine	n/a	C₁₁H₁₅NO₂	详情	详情
(XVIII)	53632	5-[(1R)-1-isocyanatobutyl]-1,3-benzodioxole; (1R)-1-(1,3-benzodioxol-5-yl)butyl isocyanate	n/a	C₁₂H₁₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVII)

Preparation of the intermediate chiral amine (XVII) was reported by a number of synthetic strategies. Piperonal (X) was condensed with D-phenylglycinol (XXIV) to give imine (XXV). Diastereoselective addition of allylmagnesium chloride (XXVI) to imine (XXV) afforded amine (XXVII). Simultaneous hydrogenation of the double bond and hydrogenolysis of the chiral auxiliary of (XXVII) furnished the desired amine (XVII).

参考文献中间体

合成目标

【1】 Storace, L.; et al.; An efficient large-scale process for the human leukocyte elastase inhibitor, DMP 777. Org Process Res Dev 2002, 6, 1, 54.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	10127	1,3-Benzodioxole-5-carbaldehyde; Heliotropine	120-57-0	C₈H₆O₃	详情	详情
(XVII)	53631	(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine	n/a	C₁₁H₁₅NO₂	详情	详情
(XXIV)	14376	(2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol	56613-80-0	C₈H₁₁NO	详情	详情
(XXV)	53637	(2R)-2-{[(E)-1,3-benzodioxol-5-ylmethylidene]amino}-2-phenyl-1-ethanol	n/a	C₁₆H₁₅NO₃	详情	详情
(XXVI)	53638	allyl(chloro)magnesium	2622-05-1	C₃H₅ClMg	详情	详情
(XXVII)	53639	(2R)-2-{[(1R)-1-(1,3-benzodioxol-5-yl)-3-butenyl]amino}-2-phenyl-1-ethanol	n/a	C₁₉H₂₁NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVII)

Addition of n-propylmagnesium chloride to piperonylonitrile (XXXII), followed by sulfinylation of the intermediate (XXXIII) with menthyl p-toluenesulfinate (XXXIV), furnished the sulfinyl imine (XXXV). Diastereoselective reduction of imine (XXXV) with DIBAL gave the desired sulfinamide (XXXVI). Amine (XVII) was then obtained by mild acidic hydrolysis of sulfinamide (XXXVI).

参考文献中间体

合成目标

【1】 Storace, L.; et al.; An efficient large-scale process for the human leukocyte elastase inhibitor, DMP 777. Org Process Res Dev 2002, 6, 1, 54.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVII)	53631	(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine	n/a	C₁₁H₁₅NO₂	详情	详情
(XXXII)	53644		n/a	C₁₁H₁₂ClMgNO₂	详情	详情
(XXXIII)	53645	(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl 4-methylbenzenesulfinate	n/a	C₁₇H₂₆O₂S	详情	详情
(XXXIV)	53646	1,3-benzodioxole-5-carbonitrile	4421-09-4	C₈H₅NO₂	详情	详情
(XXXV)	53647	N-[(E)-1-(1,3-benzodioxol-5-yl)butylidene]-4-methylbenzenesulfinamide	n/a	C₁₈H₁₉NO₃S	详情	详情
(XXXVI)	53648	N-[(1R)-1-(1,3-benzodioxol-5-yl)butyl]-4-methylbenzenesulfinamide	n/a	C₁₈H₂₁NO₃S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XVII)

The preferred synthetic route began with the Friedel-Crafts acylation of benzodioxol (XXXVII) by means of butyric anhydride and BF3. The resultant butyrophenone (XIII) was then condensed with (R)-1-phenylethylamine (XXXVII), using TiCl4 as the dehydrating reagent, to afford the E-imine (XXXIX) as the major isomer. Catalytic hydrogenation of imine (XXXIX) in the presence of Raney-Ni furnished the desired amine (XL). The chiral auxiliary was then removed by hydrogenolysis over Pd/C to yield amine (XVII).

参考文献中间体

合成目标

【1】 Storace, L.; et al.; An efficient large-scale process for the human leukocyte elastase inhibitor, DMP 777. Org Process Res Dev 2002, 6, 1, 54.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	53629	1-(1,3-benzodioxol-5-yl)-1-butanone	63740-97-6	C₁₁H₁₂O₃	详情	详情
(XVII)	53631	(1R)-1-(1,3-benzodioxol-5-yl)-1-butanamine; (1R)-1-(1,3-benzodioxol-5-yl)butylamine	n/a	C₁₁H₁₅NO₂	详情	详情
(XXVIII)	10039	(1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine	3886-69-9	C₈H₁₁N	详情	详情
(XXXVII)	50641	1,3-Dioxaindane; 1,3-Benzodioxole; methylenedioxybenzene; 1,2-methylenedioxybenzene; catechol methylene ether	274-09-9	C₇H₆O₂	详情	详情
(XXXIX)	53649	(1R)-N-[(E)-1-(1,3-benzodioxol-5-yl)butylidene]-1-phenyl-1-ethanamine; N-[(E)-1-(1,3-benzodioxol-5-yl)butylidene]-N-[(1R)-1-phenylethyl]amine	n/a	C₁₉H₂₁NO₂	详情	详情
(XL)	53650	N-[(1R)-1-(1,3-benzodioxol-5-yl)butyl]-N-[(1R)-1-phenylethyl]amine; (1R)-1-(1,3-benzodioxol-5-yl)-N-[(1R)-1-phenylethyl]-1-butanamine	n/a	C₁₉H₂₃NO₂	详情	详情

Extended Information