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【结 构 式】

【分子编号】35233

【品名】4-(2-aminoethyl)-1,3-thiazol-2-amine; 4-(2-aminoethyl)-1,3-thiazol-2-ylamine

【CA登记号】

【 分 子 式 】C5H9N3S

【 分 子 量 】143.21268

【元素组成】C 41.93% H 6.33% N 29.34% S 22.39%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VII)

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.

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:(VII)

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.

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