1,3-thiazol-2-yllithium -Drug Synthesis Database

【结构式】

【分子编号】23162

【品名】1,3-thiazol-2-yllithium

【CA登记号】

【分子式】C₃H₂LiNS

【分子量】91.06262

【元素组成】C 39.57% H 2.21% Li 7.62% N 15.38% S 35.21%

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：(IV)

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：(VIII)

Synthetic pathway for obtaining EN 292685: Treatment of amino acid (I) with CbzOSu affords the protected amino acid (II), which is further protected by means of Boc2O to yield derivative (III). Condensation of amino acid (III) with N,O-dimethyl hydroxylamine by means of BOP and DIEA provides hydroxamic ester (IV), which is then subjected to hydrogenolysis over Pd/C in CHCl3 for selective deprotection, furnishing compound (V). Coupling of (V) to intermediate (VI) affords derivative (VII), which is then coupled to lithium derivative (VIII) to give protected compound (IX). Finally, the Boc group of (IX) is removed by treatment with TFA.

参考文献中间体

合成目标

【1】 Soll, R.M.; Lu, T.; Tomczuk, B.E.; Spurlino, J.; Pan, W.; Bone, R.; Green, D.W.; Heteroaryl keto thrombin inhibitors: Design and synthesis. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 285.
【2】 Tumczuk, B.E.; Pan, W.; Soll, R.M.; Lu, T. (3-Dimensional Pharmaceuticals, Inc.); Heteroaryl protease inhibitors and diagnostic imaging agents. WO 0104117 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	44766	(2S)-2-amino-4-([[amino(imino)methyl]amino]oxy)butyric acid	C₅H₁₂N₄O₃	详情	详情
(II)	44767	5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione	C₃₈H₃₂N₄O₄S	详情	详情
(III)	44775	(11S)-11-[[(benzyloxy)carbonyl]amino]-6-imino-2,2-dimethyl-4-oxo-3,8-dioxa-5,7-diazadodecan-12-oic acid	C₁₈H₂₆N₄O₇	详情	详情
(IV)	44776	benzyl (1S)-6-imino-1-[[methoxy(methyl)amino]carbonyl]-10,10-dimethyl-8-oxo-4,9-dioxa-5,7-diazaundec-1-ylcarbamate	C₂₀H₃₁N₅O₇	详情	详情
(V)	44785	tert-butyl (6S)-6-amino-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate	C₁₂H₂₅N₅O₅	详情	详情
(VI)	44786	2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid	C₁₅H₁₅IN₂O₅S	详情	详情
(VII)	44787	tert-butyl (6S)-6-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate	C₂₇H₃₈IN₇O₉S	详情	详情
(VIII)	23162	1,3-thiazol-2-yllithium	C₃H₂LiNS	详情	详情
(IX)	44788	tert-butyl imino([[(3S)-3-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-4-oxo-4-(1,2lambda(5),3-thiadiazol-2-yl)butyl]oxy]amino)methylcarbamate	C₂₇H₃₅IN₈O₈S₂	详情	详情

Extended Information