4-cyanophenylboronic acid -Drug Synthesis Database

【结构式】

【分子编号】38835

【品名】4-cyanophenylboronic acid

【CA登记号】126747-14-6

【分子式】C₇H₆BNO₂

【分子量】146.94118

【元素组成】C 57.22% H 4.12% B 7.36% N 9.53% O 21.78%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

Mitsunobu coupling of N-Boc-3-(S)-hydroxypyrrolidine (I) with 3-bromo-2-chloro-5-hydroxypyridine (II) afforded ether (III). Subsequent introduction of the cyanophenyl group in (III) to give (V) was effected by Suzuki coupling with boronic acid (IV) in the presence of palladium catalyst. Finally, acid deprotection of the Boc group of (V) furnished the title compound.

参考文献中间体

合成目标

【1】 Shank, R.; Davis, C.; Reiltz, A.; Rivero, R.; Lee, J.; Discovery of novel pyridyl ethers as ligand for nicotinic acetylcholine receptor. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 271.
【2】 Jung, S.L. (Ortho-McNeil Pharmaceutical, Inc.); Pyridyl ethers and thioethers as ligands for nicotinic acetylcholine receptor and its therapeutic application. WO 0010997 .

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)	16286	tert-butyl (3S)-3-hydroxytetrahydro-1H-pyrrole-1-carboxylate		C₉H₁₇NO₃	详情	详情
(II)	38833	5-bromo-6-chloro-3-pyridinol		C₅H₃BrClNO	详情	详情
(III)	38834	tert-butyl (3R)-3-[(5-bromo-6-chloro-3-pyridinyl)oxy]-1-pyrrolidinecarboxylate		C₁₄H₁₈BrClN₂O₃	详情	详情
(IV)	38835	4-cyanophenylboronic acid	126747-14-6	C₇H₆BNO₂	详情	详情
(V)	38836	tert-butyl (3R)-3-[[6-chloro-5-(4-cyanophenyl)-3-pyridinyl]oxy]-1-pyrrolidinecarboxylate		C₂₁H₂₂ClN₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The compound has also been obtained by solid phase synthesis. Attachment of (S)-3-hydroxypyrrolidine (VII) to p-nitrophenylcarbonate Wang resin (VI) in the presence of diisopropylethylamine provided the resin bound pyrrolidinol (VIII). Coupling of (VIII) with 3-bromo-2-chloro-5-hydroxypyridine (II) under Mitsunobu conditions gave resin (IX). Further Suzuki coupling of (IX) with 4-cyanophenylboronic acid (IV) afforded (X). The title compound was then cleaved from the resin (X) by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Shank, R.; Davis, C.; Reiltz, A.; Rivero, R.; Lee, J.; Discovery of novel pyridyl ethers as ligand for nicotinic acetylcholine receptor. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 271.
【2】 Davis, C.B.; Shank, R.P.; Reitz, A.B.; Lee, J.; Rivero, R.A.; Synthesis and structure-activity relationship of novel pyridyl ethers for the nicotinic acetylcholine receptor. Bioorg Med Chem Lett 2000, 10, 10, 1063.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	38833	5-bromo-6-chloro-3-pyridinol		C₅H₃BrClNO	详情	详情
(IV)	38835	4-cyanophenylboronic acid	126747-14-6	C₇H₆BNO₂	详情	详情
(VI)	38837	4-nitrophenyl hydrogen carbonate		C₇H₅NO₅	详情	详情
(VII)	38841	(3R)-3-pyrrolidinol		C₄H₉NO	详情	详情
(VIII)	38838	(3R)-3-hydroxy-1-pyrrolidinecarboxylic acid		C₅H₉NO₃	详情	详情
(IX)	38839	(3R)-3-[(5-bromo-6-chloro-3-pyridinyl)oxy]-1-pyrrolidinecarboxylic acid		C₁₀H₁₀BrClN₂O₃	详情	详情
(X)	38840	(3R)-3-[[6-chloro-5-(4-cyanophenyl)-3-pyridinyl]oxy]-1-pyrrolidinecarboxylic acid		C₁₇H₁₄ClN₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

Methylation of (4-bromophenyl)acetonitrile (I) to afford 2-(4-bromophenyl)propionitrile (III) was carried out by heating with K2CO3 and dimethyl carbonate at 180 C in a sealed vessel. Alternatively, nitrile (III) was obtained by treatment of 4'-bromoacetophenone (II) with tosylmethyl isocyanide and potassium tert-butoxide. Nitrile (III) was reduced to amine (IV) using borane-dimethyl sulfide complex. Condensation of this amine with isopropylsulfonyl chloride furnished the corresponding sulfonamide (V). 4-Cyanophenylboronic acid (VII) was obtained by lithiation of 4-bromobenzonitrile (VI), followed by treatment with triisopropyl borate. Then, Suzuki coupling of boronic acid (VII) with bromide (V) furnished the title compound.

参考文献中间体

合成目标

【1】 Nakamura, J.; Kuwana, Y.; Kitamura, S.; Ichikawa, S.; Yamada, K.; Ornstein, P.L.; Biarylpropylsulfonamides as novel, potent potentiators of 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)-propanoic acid (AMPA) receptors. J Med Chem 2000, 43, 23, 4354.
【3】 Ornstein, P.L.; Jones, W.D.; Zarrinmayeh, H.; Zimmerman, D.M.; Arnold, M.B. (Eli Lilly and Company); N-Substd. sulfonamide derivs.. WO 0006537 .
【2】 Arnold, M.B.; Bleakman, D.; Simon, R.L.; Cantrell, B.E.; Ornstein, P.L.; McKennon, T.E.; Tizzano, J.P.; Bleisch, T.J.; Zimmerman, D.M.; Baker, S.R.; Smith, E.; Zarrinmayeh, H.; Matsumoto, K.; Escribano, A.M. (Eli Lilly and Company); Sulphonamide derivs.. EP 0860428; WO 9833496 .

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)	45829	2-(4-bromophenyl)acetonitrile; 4-Bromobenzyl cyanide	16532-79-9	C₈H₆BrN	详情	详情
(II)	25421	1-(4-bromophenyl)-1-ethanone	99-90-1	C₈H₇BrO	详情	详情
(III)	45830	2-(4-bromophenyl)propanenitrile		C₉H₈BrN	详情	详情
(IV)	45831	2-(4-bromophenyl)propylamine; 2-(4-bromophenyl)-1-propanamine		C₉H₁₂BrN	详情	详情
(V)	45832	N-[2-(4-bromophenyl)propyl]-2-propanesulfonamide		C₁₂H₁₈BrNO₂S	详情	详情
(VI)	45833	4-Bromobenzonitrile	623-00-7	C₇H₄BrN	详情	详情
(VII)	38835	4-cyanophenylboronic acid	126747-14-6	C₇H₆BNO₂	详情	详情

Extended Information