2-(3-oxobutyl)-1H-isoindole-1,3(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】35230

【品名】2-(3-oxobutyl)-1H-isoindole-1,3(2H)-dione

【CA登记号】

【分子式】C₁₂H₁₁NO₃

【分子量】217.22428

【元素组成】C 66.35% H 5.1% N 6.45% O 22.1%

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：(III)

Michael addition of methyl vinyl ketone (II) to phthalimide (I) in the presence of NaOEt afforded phthalimido ketone (III). Bromination of (III) in MeOH, followed by acid hydrolysis of the resulting dimethyl ketal provided bromo ketone (IV). Cyclization of bromo ketone (IV) with thiourea (V) yielded the amino thiazole (VI) and further deprotection of the phthalimido group of (VI) in refluxing HBr furnished diamine (VII). 3,4,5-Trimethoxyphenylacetic acid (VIII) was converted to the corresponding acid chloride (IX) using oxalyl chloride, and subsequently coupled with amine (VII) under Schotten-Baumann conditions to give amide (X). Cyclization of (X) to the thiazolopyridine (XI) was effected by the Bischler-Napieralski procedure employing POCl3 in acetonitrile. The imine double bond of (XI) was then reduced by means of NaBH4, and the resulting compound was finally converted to the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Shams, G.; Feller, D.R.; Zheng, W.; Konkar, A.A.; Miller, D.D.; Nikulin, V.I.; Vansal, S.S.; 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines: Novel selective beta3-adrenoceptor agonists. J Med Chem 1999, 42, 12, 2287.
【2】 Miller, D.D.; Feller, D.R. (Molecular Design International, Inc. ); beta3-Adrenoreceptor agonists, agonist compsns. and methods of using. EP 1023269; WO 9916752 .

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)	12376	Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione	85-41-6	C₈H₅NO₂	详情	详情
(II)	30324	3-buten-2-one; methyl vinyl ketone	78-94-4	C₄H₆O	详情	详情
(III)	35230	2-(3-oxobutyl)-1H-isoindole-1,3(2H)-dione		C₁₂H₁₁NO₃	详情	详情
(IV)	35231	2-(4-bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dione		C₁₂H₁₀BrNO₃	详情	详情
(V)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VI)	35232	2-[2-(2-amino-1,3-thiazol-4-yl)ethyl]-1H-isoindole-1,3(2H)-dione		C₁₃H₁₁N₃O₂S	详情	详情
(VII)	35233	4-(2-aminoethyl)-1,3-thiazol-2-amine; 4-(2-aminoethyl)-1,3-thiazol-2-ylamine		C₅H₉N₃S	详情	详情
(VIII)	25349	2-(3,4,5-trimethoxyphenyl)acetic acid	937-52-0	C₁₁H₁₄O₅	详情	详情
(IX)	35238	2-(3,4,5-trimethoxyphenyl)acetyl chloride		C₁₁H₁₃ClO₄	详情	详情
(X)	35239	N-[2-(2-amino-1,3-thiazol-4-yl)ethyl]-2-(3,4,5-trimethoxyphenyl)acetamide		C₁₆H₂₁N₃O₄S	详情	详情
(XI)	35240	4-(3,4,5-trimethoxybenzyl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-2-amine; 4-(3,4,5-trimethoxybenzyl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-2-ylamine		C₁₆H₁₉N₃O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Michael addition of methyl vinyl ketone (II) to phthalimide (I) in the presence of NaOEt afforded phthalimido ketone (III). Bromination of (III) in MeOH, followed by acid hydrolysis of the resulting dimethyl ketal provided bromo ketone (IV). Cyclization of bromo ketone (IV) with thiourea (V) yielded the amino thiazole (VI) and further deprotection of the phthalimido group of (VI) in refluxing HBr furnished diamine (VII). 3,5-Diiodo-4-methoxyphenylacetic acid (VIII) was converted to the corresponding acid chloride (IX) using oxalyl chloride, and subsequently coupled with amine (VII) under Schotten-Baumann conditions to give amide (X). Cyclization of (X) to the thiazolopyridine (XI) was effected by the Bischler-Napieralski procedure employing POCl3 in acetonitrile. The imine double bond of (XI) was then reduced by means of NaBH4, and the resulting compound was finally converted to the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Shams, G.; Feller, D.R.; Zheng, W.; Konkar, A.A.; Miller, D.D.; Nikulin, V.I.; Vansal, S.S.; 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines: Novel selective beta3-adrenoceptor agonists. J Med Chem 1999, 42, 12, 2287.
【2】 Miller, D.D.; Feller, D.R. (Molecular Design International, Inc. ); beta3-Adrenoreceptor agonists, agonist compsns. and methods of using. EP 1023269; WO 9916752 .

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)	12376	Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione	85-41-6	C₈H₅NO₂	详情	详情
(II)	30324	3-buten-2-one; methyl vinyl ketone	78-94-4	C₄H₆O	详情	详情
(III)	35230	2-(3-oxobutyl)-1H-isoindole-1,3(2H)-dione		C₁₂H₁₁NO₃	详情	详情
(IV)	35231	2-(4-bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dione		C₁₂H₁₀BrNO₃	详情	详情
(V)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VI)	35232	2-[2-(2-amino-1,3-thiazol-4-yl)ethyl]-1H-isoindole-1,3(2H)-dione		C₁₃H₁₁N₃O₂S	详情	详情
(VII)	35233	4-(2-aminoethyl)-1,3-thiazol-2-amine; 4-(2-aminoethyl)-1,3-thiazol-2-ylamine		C₅H₉N₃S	详情	详情
(VIII)	35234	2-(3,5-diiodo-4-methoxyphenyl)acetic acid		C₉H₈I₂O₃	详情	详情
(IX)	35235	2-(3,5-diiodo-4-methoxyphenyl)acetyl chloride		C₉H₇ClI₂O₂	详情	详情
(X)	35236	N-[2-(2-amino-1,3-thiazol-4-yl)ethyl]-2-(3,5-diiodo-4-methoxyphenyl)acetamide		C₁₄H₁₅I₂N₃O₂S	详情	详情
(XI)	35237	4-(3,5-diiodo-4-methoxybenzyl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-2-amine; 4-(3,5-diiodo-4-methoxybenzyl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-2-ylamine		C₁₄H₁₃I₂N₃OS	详情	详情

Extended Information