2-Amino-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide -Drug Synthesis Database

【结构式】

【分子编号】12928

【品名】2-Amino-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide

【CA登记号】

【分子式】C₂₆H₂₉ClN₂O₂S

【分子量】469.04724

【元素组成】C 66.58% H 6.23% Cl 7.56% N 5.97% O 6.82% S 6.84%

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：(VI)

Reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur in DMF/NEt3 gives 2-amino-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl)ethyl]thiophene (III), which is acylated with 2-chloropropionyl chloride (IV) in chloroform to give 2-(2-chloropropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (V). Compound (V) is treated with sodium iodide in THF followed by liquid ammonia to give 2-(2-aminopropionamido)-3-(2-chlorobenzoyl)-5-[2-(4-isobutylphenyl) ethyl]thiophene (VI), which is cyclized in isopropanol and acetic acid to give 5-(2-chlorophenyl)-5-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-one (VII). Compound (VII) gives 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1H-thieno[2,3-e]-1,4-diazepin-2-thione (VIII) upon treatment with Lawesson's reagent. Finally, (VIII) is cyclized with hydrazine hydrate and ethyl orthoformiate.

参考文献中间体

合成目标

【1】 Tahara, T.; Moriwaki, M.; Abe, M.; Yuasa, S. (Welfide Corporation); PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical uses thereof. EP 0268242; JP 1989156982; US 4820703 .
【2】 Castaner, J.; Prous, J.; Mealy, N.; Y-24180. Drugs Fut 1993, 18, 11, 1016.

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)	12923	3-(2-Chlorophenyl)-3-oxopropanenitrile	40018-25-5	C₉H₆ClNO	详情	详情
(II)	12924	4-(4-Isobutylphenyl)butanal		C₁₄H₂₀O	详情	详情
(III)	12925	[2-Amino-5-(4-isobutylphenethyl)-3-thienyl](2-chlorophenyl)methanone		C₂₃H₂₄ClNOS	详情	详情
(IV)	12926	2-Chloropropanoyl chloride; 2-Chloropropionyl chloride	7623-09-8	C₃H₄Cl₂O	详情	详情
(V)	12927	2-Chloro-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide		C₂₆H₂₇Cl₂NO₂S	详情	详情
(VI)	12928	2-Amino-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide		C₂₆H₂₉ClN₂O₂S	详情	详情
(VII)	12929	5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one		C₂₆H₂₇ClN₂OS	详情	详情
(VIII)	12930	5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepine-2-thione		C₂₆H₂₇ClN₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

A new synthesis of Y-24180 has been published: The reaction of 2-(2-chlorobenzoyl)acetonitrile (I) with 4-(4-isobutylphenyl)butyraldehyde (II) and sulfur by means of triethylamine in DMF gives the benzoylthiophene (III), which is condensed with 2-phthalimidopropionyl chloride (IV) yielding the propionamidothiophene (V). Elimination of the phthalimido group of (V) first with hydrazine and then with HCl affords the alanylaminothiophene (VI), which is cyclized by means of acetic acid giving 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-2,3-dihydro-1 H-thieno[3,2-f][1,4]diazepin-2-one (VII). The reaction of (VII) with P2S5 yields the corresponding thioketone (VIII), which by reaction with hydrazine is converted into the hydrazone (IX). Finally, this compound is cyclized with triethyl orthoacetate (X).

参考文献中间体

合成目标

【1】 Kawakami, Y.; Moriwaki, M.; Kitani, H.; Kagoshima, M.; Abe, M.; Tahara, T.; Terasawa, M.; Yuasa, S.; Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1, 2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: Pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system. Eur J Med Chem 1996, 31, 9, 683.

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)	12923	3-(2-Chlorophenyl)-3-oxopropanenitrile	40018-25-5	C₉H₆ClNO	详情	详情
(II)	12924	4-(4-Isobutylphenyl)butanal		C₁₄H₂₀O	详情	详情
(III)	12925	[2-Amino-5-(4-isobutylphenethyl)-3-thienyl](2-chlorophenyl)methanone		C₂₃H₂₄ClNOS	详情	详情
(IV)	12934	2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl chloride		C₁₁H₈ClNO₃	详情	详情
(V)	12935	N-[3-(2-Chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanamide		C₃₄H₃₁ClN₂O₄S	详情	详情
(VI)	12928	2-Amino-N-[3-(2-chlorobenzoyl)-5-(4-isobutylphenethyl)-2-thienyl]propanamide		C₂₆H₂₉ClN₂O₂S	详情	详情
(VII)	12929	5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one		C₂₆H₂₇ClN₂OS	详情	详情
(VIII)	12930	5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepine-2-thione		C₂₆H₂₇ClN₂S₂	详情	详情
(IX)	12939	5-(2-Chlorophenyl)-7-(4-isobutylphenethyl)-3-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one hydrazone		C₂₆H₂₉ClN₄S	详情	详情
(X)	12940	1,1-Diethoxyethyl ethyl ether; 1,1,1-Triethoxyethane; Triethyl orthoacetate	78-39-7	C₈H₁₈O₃	详情	详情

Extended Information