tert-butyl 4-iodo-3-pyridinylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】35571

【品名】tert-butyl 4-iodo-3-pyridinylcarbamate

【CA登记号】

【分子式】C₁₀H₁₃IN₂O₂

【分子量】320.12997

【元素组成】C 37.52% H 4.09% I 39.64% N 8.75% O 10%

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：(X)

3-(tert-Butoxycarbonylamino)-2-pyrrolidinone (II), obtained by cyclization of (S)-Boc-2,4-diaminobutyric acid (I) in the presence of EDC, was regioselectively alkylated with propargyl bromide and NaH to give the N-propargyl pyrrolidinone (III). Subsequent acid-promoted deprotection of the Boc group of (III) provided aminopyrrolidinone (IV). Sulfonyl chloride (VII) was prepared by lithiation of thienopyridine (V), followed by addition of SO2, and further chlorination of the resulting sulfinic acid (VI) with sulfuryl chloride. This sulfonyl chloride (VII) was then coupled with aminopyrrolidinone (III), yielding sulfonamide (VIII). Lithiation of 3-(tert-butoxycarbonylamino)pyridine (IX) and subsequent treatment with iodine in cold THF provided the iodopyridine derivative (X). Palladium-mediated coupling of (X) with propargyl pyrrolidinone (VIII) furnished adduct (XI), which was cyclized to the pyrrolopyridine system (XII) upon treatment with DBU. Finally, the Boc protecting group of (XII) was removed using trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Choi-Sledeski, Y.M.; Becker, M.R.; Pauls, H.W.; et al.; Azaindole pyrrolidinone inhibitors of factor Xa: SAR, synthesis, and X-ray crystal structure of a novel surrogate for basic P1 moieties. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 33.
【2】 Choi-Sledeski, Y.M.; Pauls, H.W.; Green, D.M.; Barton, J.N.; Becker, M.R.; Ewing, W.R. (Aventis Pharmaceuticals, Inc.); Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide cpds.. EP 0944386; WO 9825611 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(I)	29493	(2S)-4-amino-2-[(tert-butoxycarbonyl)amino]butyric acid		C₉H₁₈N₂O₄	详情	详情
(II)	29492	tert-butyl (3S)-2-oxopyrrolidinylcarbamate		C₉H₁₆N₂O₃	详情	详情
(III)	35566	tert-butyl (3S)-2-oxo-1-(2-propynyl)pyrrolidinylcarbamate		C₁₂H₁₈N₂O₃	详情	详情
(IV)	35567	(3S)-3-amino-1-(2-propynyl)-2-pyrrolidinone		C₇H₁₀N₂O	详情	详情
(V)	29500	thieno[3,2-b]pyridine		C₇H₅NS	详情	详情
(VI)	35568	thieno[3,2-b]pyridine-2-sulfonic acid		C₇H₅NO₃S₂	详情	详情
(VII)	29496	thieno[3,2-b]pyridine-2-sulfonyl chloride		C₇H₄ClNO₂S₂	详情	详情
(VIII)	35569	N-[(3S)-2-oxo-1-(2-propynyl)pyrrolidinyl]thieno[3,2-b]pyridine-2-sulfonamide		C₁₄H₁₃N₃O₃S₂	详情	详情
(IX)	35570	tert-butyl 3-pyridinylcarbamate	56700-70-0	C₁₀H₁₄N₂O₂	详情	详情
(X)	35571	tert-butyl 4-iodo-3-pyridinylcarbamate		C₁₀H₁₃IN₂O₂	详情	详情
(XI)	35572	tert-butyl 4-(3-[(3S)-2-oxo-3-[(thieno[3,2-b]pyridin-2-ylsulfonyl)amino]pyrrolidinyl]-1-propynyl)-3-pyridinylcarbamate		C₂₄H₂₅N₅O₅S₂	详情	详情
(XII)	35573	tert-butyl 2-([(3S)-2-oxo-3-[(thieno[3,2-b]pyridin-2-ylsulfonyl)amino]pyrrolidinyl]methyl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate		C₂₄H₂₅N₅O₅S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

N-alkylation of (S)-3-(benzyloxycarbonylamino)-2-pyrrolidinone (XIII) with propargyl bromide produced (XIV). Palladium-mediated coupling (XIV) with iodopyridine (X) gave adduct (XV), which was cyclized to the pyrrolopyridine (XVI) by means of DBU. The benzyloxycarbonyl protecting group of (XVI) was removed by transfer catalytic hydrogenolysis with formic acid, and the deprotected amine (XVII) was then condensed with sulfonyl chloride (VII) to furnish sulfonamide (XII). Deprotection of the Boc group of (XII) as above gave rise to the title compound.

参考文献中间体

合成目标

【1】 Choi-Sledeski, Y.M.; Becker, M.R.; Pauls, H.W.; et al.; Azaindole pyrrolidinone inhibitors of factor Xa: SAR, synthesis, and X-ray crystal structure of a novel surrogate for basic P1 moieties. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 33.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(VII)	29496	thieno[3,2-b]pyridine-2-sulfonyl chloride		C₇H₄ClNO₂S₂	详情	详情
(X)	35571	tert-butyl 4-iodo-3-pyridinylcarbamate		C₁₀H₁₃IN₂O₂	详情	详情
(XII)	35573	tert-butyl 2-([(3S)-2-oxo-3-[(thieno[3,2-b]pyridin-2-ylsulfonyl)amino]pyrrolidinyl]methyl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate		C₂₄H₂₅N₅O₅S₂	详情	详情
(XIII)	35574	benzyl (3S)-2-oxopyrrolidinylcarbamate		C₁₂H₁₄N₂O₃	详情	详情
(XIV)	35575	benzyl (3S)-2-oxo-1-(2-propynyl)pyrrolidinylcarbamate		C₁₅H₁₆N₂O₃	详情	详情
(XV)	35576	benzyl (3S)-1-(3-[3-[(tert-butoxycarbonyl)amino]-4-pyridinyl]-2-propynyl)-2-oxopyrrolidinylcarbamate		C₂₅H₂₈N₄O₅	详情	详情
(XVI)	35577	tert-butyl 2-[((3S)-3-[[(benzyloxy)carbonyl]amino]-2-oxopyrrolidinyl)methyl]-1H-pyrrolo[2,3-c]pyridine-1-carboxylate		C₂₅H₂₈N₄O₅	详情	详情
(XVII)	35578	tert-butyl 2-[[(3S)-3-amino-2-oxopyrrolidinyl]methyl]-1H-pyrrolo[2,3-c]pyridine-1-carboxylate		C₁₇H₂₂N₄O₃	详情	详情

Extended Information