N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine -Drug Synthesis Database

【结构式】

【分子编号】12361

【品名】N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine

【CA登记号】103-49-1

【分子式】C₁₄H₁₅N

【分子量】197.27984

【元素组成】C 85.24% H 7.66% N 7.1%

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：(II)

The intermediate 3-(2-aminoethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (IV) has been obtained as follows: The condensation of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (I) with dibenzylamine (II) by means of NaHCO3 in refluxing acetonitrile gives the tertiary amine (III), which is debenzylated by hydrogenation with H2 over Pd/C in warm ethanol to afford the target intermediate (IV).

参考文献中间体

合成目标

【1】 Huguet-Clotet, J.; Marquillas Olondriz, F.; Caldero Ges, J.M.; Del Castillo Nieto, J.C.; Dalmases Barjoan, P.; Bosch Rovira, A. (Vita-Invest, SA); Process for obtaining 3-2-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-ethyl-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]pyrimidine-4-one. ES 2074966 .

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)	23044	3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one	63234-80-0	C₁₁H₁₅ClN₂O	详情	详情
(II)	12361	N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine	103-49-1	C₁₄H₁₅N	详情	详情
(III)	50858	3-[2-(dibenzylamino)ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one		C₂₅H₂₉N₃O	详情	详情
(IV)	50859	3-(2-aminoethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one		C₁₁H₁₇N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

2) The reaction of N-(2,3-epoxypropyl)phthalimide (I) with dibenzylamine (II) at 80 C gives 1-(dibenzylamino)-3-(phthalimido)-2-propanol (III), which is hydrolyzed with refluxing concentrated HCl to afford 1-amino-3-(dibenzylamino)-2-propanol (IV). The acylation of (IV) with chloroacetyl chloride (V) in CHCl3 yields the corresponding chloroacetamide (VI), which is cyclized by means of potassium tert-butoxide in refluxing ethanol to give 6-(dibenzylaminomethyl)morpholin-3-one (VII). The debenzylation of (VII) with H2 over Pd(OH)2/C in ethanol yields 6-(aminomethyl)morpholin-3-one (VIII), which is condensed with 4-(acetamido)-5-chloro-2-ethoxybenzoyl chloride (IX) by means of triethylamine in CHCl3 to afford the monoacetylated derivative of metabolite M-2 (X). Finally, this compound is hydrolyzed with HCl in refluxing ethanol/water to give metabolite M-2. The two final steps of this sequence can also be performed in a single step by condensation of morpholinone (VIII) with 4-amino-5-chloro-2-ethoxybenzoic acid (XI) by means of carbonyldiimidazole (CDI) in THF to afford directly the metabolite M-2 after neutralization with aqueous NH4OH.

参考文献中间体

合成目标

【1】 Kato, S.; Yoshida, N.; Morie, T.; Synthesis and biological activities of metabolites of mosapride, a new gastroprokinetic agent. Chem Pharm Bull 1995, 43, 4, 699.

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)	12335	2-(2-Oxiranylmethyl)-1H-isoindole-1,3(2H)-dione; N-(2,3-Epoxypropyl)phtalimide	5455-98-1	C₁₁H₉NO₃	详情	详情
(II)	12361	N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine	103-49-1	C₁₄H₁₅N	详情	详情
(III)	12362	2-[3-(Dibenzylamino)-2-hydroxypropyl]-1H-isoindole-1,3(2H)-dione		C₂₅H₂₄N₂O₃	详情	详情
(IV)	12363	1-Amino-3-(dibenzylamino)-2-propanol		C₁₇H₂₂N₂O	详情	详情
(V)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(VI)	12365	2-Chloro-N-[3-(dibenzylamino)-2-hydroxypropyl]acetamide		C₁₉H₂₃ClN₂O₂	详情	详情
(VII)	12366	6-[(Dibenzylamino)methyl]-3-morpholinone		C₁₉H₂₂N₂O₂	详情	详情
(VIII)	12367	6-(Aminomethyl)-3-morpholinone		C₅H₁₀N₂O₂	详情	详情
(IX)	12368	4-(Acetamido)-5-chloro-2-ethoxybenzoyl chloride		C₁₁H₁₁Cl₂NO₃	详情	详情
(X)	12369	4-(Acetamido)-5-chloro-2-ethoxy-N-[(5-oxo-1,4-oxazinan-2-yl)methyl]benzamide		C₁₆H₂₀ClN₃O₅	详情	详情
(XI)	12333	4-Amino-5-chloro-2-ethoxybenzoic acid		C₉H₁₀ClNO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IX)

The condensation of tert-butyl 4-iodobenzoate (I) with N-(3-butenyl)phthalimide (II) by means of palladium acetate and tri-p-tolylphosphine in TEA at 110 C gives 4-(4-phthalimido-1-butenyl)benzoic acid tert-butyl ester (III), which is hydrogenated with H2 over Pd/C in THF/ethanol yielding the corresponding butyl derivative (IV). The treatment of (IV) with hydrazine in refluxing ethanol affords 4-(4-aminobutyl)benzoic acid tert-butyl ester (V), which is cyclized with 2-sulfanylsuccinic acid (VI) and octanal (VII) in refluxing toluene to provide the thiazolidinone (VIII). The condensation of (VIII) with dibenzylamine (IX) by means of HOBT and EDC in dichloromethane, followed by chromatographic separation of the undesired (2R*,5S*)-isomer, yields the (2S*,5S*)-dibenzylamide (X). Finally, this compound is hydrolyzed with TFA in dichloromethane affording the target benzoic acid.

参考文献中间体

合成目标

【1】 Willson, T.M.; Holmes, C.P.; Collins, J.L.; Lenhard, J.M. (Glaxo Group Ltd.); PPARgamma ligands. WO 0027832 .

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)	38028	tert-butyl 4-iodobenzoate		C₁₁H₁₃IO₂	详情	详情
(II)	38029	2-(3-butenyl)-1H-isoindole-1,3(2H)-dione	52898-32-5	C₁₂H₁₁NO₂	详情	详情
(III)	38030	tert-butyl 4-[(E)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-butenyl]benzoate		C₂₃H₂₃NO₄	详情	详情
(IV)	38031	tert-butyl 4-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]benzoate		C₂₃H₂₅NO₄	详情	详情
(V)	38032	tert-butyl 4-(4-aminobutyl)benzoate		C₁₅H₂₃NO₂	详情	详情
(VI)	38033	2-sulfanylsuccinic acid	70-49-5	C₄H₆O₄S	详情	详情
(VII)	25714	octanal	124-13-0	C₈H₁₆O	详情	详情
(VIII)	38034	2-((2S,5R)-3-[4-[4-(tert-butoxycarbonyl)phenyl]butyl]-2-heptyl-4-oxo-1,3-thiazolidin-5-yl)acetic acid		C₂₇H₄₁NO₅S	详情	详情
(IX)	12361	N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine	103-49-1	C₁₄H₁₅N	详情	详情
(X)	38035	tert-butyl 4-(4-[(2S,5R)-5-[2-(dibenzylamino)-2-oxoethyl]-2-heptyl-4-oxo-1,3-thiazolidin-3-yl]butyl)benzoate		C₄₁H₅₄N₂O₄S	详情	详情

Extended Information