2-bromo-1,3-thiazole -Drug Synthesis Database

【结构式】

【分子编号】23161

【品名】2-bromo-1,3-thiazole

【CA登记号】3034-53-5

【分子式】C₃H₂BrNS

【分子量】164.02562

【元素组成】C 21.97% H 1.23% Br 48.71% N 8.54% S 19.55%

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)

Treatment of protected lysine (I) with N,O-dimethyl hydroxylamine and (benzotriazolyl)tetramethyluronium fluoborate afforded hydroxamate (II). This was condensed with organolithium reagent (IV) (prepared from 2-bromothiazole (III) and butyllithium), to yield thiazolyl ketone (V). Acid deprotection of the N-Boc group of (V) provided amine (VI), which was then coupled with the mixed anhydride obtained from dipeptide (VII) and isobutyl chloroformate. The resulting compound (VIII) was finally deprotected using TFA and thioanisole.

参考文献中间体

合成目标

【1】 Rewinkel, J.B.M.; Smit, M.J.; Noach, A.B.J.; van Dinther, T.G.; Grootenhuis, P.D.J.; Peters, J.A.M.; Kelser, J.; Visser, A.; van Boeckel, C.A.A.; Vogel, G.M.T.; van Aelst, S.F.; Adang, A.E.P.; A polar pharmacophore for oral bioavailability in thrombin inhibitors. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.157.

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)	23159	(2S)-6-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]hexanoic acid		C₁₉H₂₈N₂O₆	详情	详情
(II)	23160	benzyl (5S)-5-[(tert-butoxycarbonyl)amino]-6-[methoxy(methyl)amino]-6-oxohexylcarbamate		C₂₁H₃₃N₃O₆	详情	详情
(III)	23161	2-bromo-1,3-thiazole	3034-53-5	C₃H₂BrNS	详情	详情
(IV)	23162	1,3-thiazol-2-yllithium		C₃H₂LiNS	详情	详情
(V)	23163	benzyl (5S)-5-[(tert-butoxycarbonyl)amino]-6-oxo-6-(1,3-thiazol-2-yl)hexylcarbamate		C₂₂H₂₉N₃O₅S	详情	详情
(VI)	23164	benzyl (5S)-5-amino-6-oxo-6-(1,3-thiazol-2-yl)hexylcarbamate		C₁₇H₂₁N₃O₃S	详情	详情
(VII)	23165	(2S)-1-((2R)-2-[(tert-butoxycarbonyl)[2-(tert-butoxy)-2-oxoethyl]amino]-3-cyclohexylpropanoyl)-2-pyrrolidinecarboxylic acid		C₂₅H₄₂N₂O₇	详情	详情
(VIII)	23166	tert-butyl 2-[[(1R)-2-[(2S)-2-([[(1S)-5-[[(benzyloxy)carbonyl]amino]-1-(1,3-thiazol-2-ylcarbonyl)pentyl]amino]carbonyl)pyrrolidinyl]-1-(cyclohexylmethyl)-2-oxoethyl](tert-butoxycarbonyl)amino]acetate		C₄₂H₆₁N₅O₉S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

4-Bromobenzaldehyde dimethyl acetal (I) was converted to the corresponding Grignard reagent and then coupled with 2-bromothiazole (II) in the presence of [1,3-bis(diphenylphosphino)propane]nickel chloride to afford 4-(2-thiazolyl)benzaldehyde dimethylacetal (III). After acid hydrolysis of the acetal group of (II), the resulting aldehyde was condensed with tert-butyl carbazate to give hydrazone (IV), which was further reduced to the benzylhydrazine (V) employing NaBH3CN and p-toluenesulfonic acid. Opening of the Boc-protected epoxide (VI) with hydrazine (V) gave hydrazinoalcohol (VII). Both Boc groups of (VII) were removed by treatment with formic acid to yield diamino compound (VIII). Finally, coupling of (VIII) with N-methoxycarbonyl-L-tert-leucine (IX) by means of O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetra fluoroborate (TPTU) provided the title bisamide.

参考文献中间体

合成目标

【1】 New aza-dipeptide analogues as potent and orally a. J Med Chem 1998, 41, 18, 3387.
【2】 Fassler, A.; Bold, G.; Capraro, H.-G.; Lang, M.; Khanna, S.C. (Novartis AG); Antivirally active heterocyclic azahexane derivs.. EP 0900210; JP 1999511177; US 5849911; WO 9740029 .

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)	23438	(4-bromophenyl)(methoxy)methyl methyl ether; 1-bromo-4-(dimethoxymethyl)benzene		C₉H₁₁BrO₂	详情	详情
(II)	23161	2-bromo-1,3-thiazole	3034-53-5	C₃H₂BrNS	详情	详情
(III)	28434	2-[4-(dimethoxymethyl)phenyl]-1,3-thiazole		C₁₂H₁₃NO₂S	详情	详情
(IV)	28435	tert-butyl 2-[(Z)-[4-(1,3-thiazol-2-yl)phenyl]methylidene]-1-hydrazinecarboxylate		C₁₅H₁₇N₃O₂S	详情	详情
(V)	28436	tert-butyl 2-[4-(1,3-thiazol-2-yl)benzyl]-1-hydrazinecarboxylate		C₁₅H₁₉N₃O₂S	详情	详情
(VI)	23444	tert-butyl (1S)-1-[(2R)oxiranyl]-2-phenylethylcarbamate		C₁₅H₂₁NO₃	详情	详情
(VII)	28437	tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(1,3-thiazol-2-yl)benzyl]-1-hydrazinecarboxylate		C₃₀H₄₀N₄O₅S	详情	详情
(VIII)	28438	(2S,3S)-3-amino-4-phenyl-1-[1-[4-(1,3-thiazol-2-yl)benzyl]hydrazino]-2-butanol		C₂₀H₂₄N₄OS	详情	详情
(IX)	23447	(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutyric acid		C₈H₁₅NO₄	详情	详情

Extended Information