3-pyridinylboronic acid -Drug Synthesis Database

【结构式】

【分子编号】38825

【品名】3-pyridinylboronic acid

【CA登记号】1692-25-7

【分子式】C₅H₆BNO₂

【分子量】122.91918

【元素组成】C 48.86% H 4.92% B 8.8% N 11.4% O 26.03%

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：(VII)

3-Fluoro-5-(3-pyridyl)aniline (IX) was prepared by palladium coupling of 3-fluoro-5-iodonitrobenzene (VI) and 3-pyridylboronic acid (VII), followed by reduction of the resultant nitro derivative (VIII) using stannous chloride in aqueous HCl (3). Treatment of aniline (IX) with phenyl chloroformate in the presence of triethylamine gave rise to carbamate (X). This was then coupled with indoline (V) to furnish the title amide.

参考文献中间体

合成目标

【1】 Gaster, L.M.; Wyman, P.A.; Mulholland, K.R.; Davies, D.T.; Duckworth, D.M.; Forbes, I.T.; Jones, G.E. (SmithKline Beecham plc); Indole derivs. as 5-HT receptor antagonist. EP 0808312; JP 1998513442; US 5990133; WO 9623783 .
【2】 Dabbs, S.; Davies, D.T.; Bromidge, S.M.; et al.; Biarylcarbamoylindolines are novel and selective 5-HT2C receptor inverse agonists: Identification of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent. J Med Chem 2000, 43, 6, 1123.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	29604	methyl 6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl ether; 5-methoxy-6-(trifluoromethyl)indoline		C₁₀H₁₀F₃NO	详情	详情
(VI)	38824	1-fluoro-3-iodo-5-nitrobenzene		C₆H₃FINO₂	详情	详情
(VII)	38825	3-pyridinylboronic acid	1692-25-7	C₅H₆BNO₂	详情	详情
(VIII)	38826	3-(3-fluoro-5-nitrophenyl)pyridine		C₁₁H₇FN₂O₂	详情	详情
(IX)	38827	3-fluoro-5-(3-pyridinyl)phenylamine; 3-fluoro-5-(3-pyridinyl)aniline		C₁₁H₉FN₂	详情	详情
(X)	38828	phenyl 3-fluoro-5-(3-pyridinyl)phenylcarbamate		C₁₈H₁₃FN₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Condensation of 2-amino-4-iodobenzoic acid (I) with 2-chloronicotinic acid (II) in refluxing EtOH in the presence of HCl yields pyridoquinazoline acid derivative (III), which is then condensed with N,N-dimethylethylenediamine (IV) in CH2Cl2 using BOP as coupling reagent to provide (V). Reaction of 2-bromopyridine (VI) in Et2O with n-BuLi and trimethylborate, followed by treatment with EtOH and HOAc, gives 3-pyridinyl boronic acid (VII), which is finally coupled to (V) in an Na2CO3 solution via a Suzuki coupling catalyzed by Pd(PPh3)4.

参考文献中间体

合成目标

【1】 Kitchen, D.B.; Schow, S.R.; Casscles, W.T. Jr.; Discafani, C.; Trova, M.P.; Lassota, P.; Zhang, N.; Powell, D.W.; Hetero biarylpyridoquinazolinone derivatives as anticancer agents. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 59.
【2】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. EP 0944628; WO 9823617 .
【3】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. US 5908840 .

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)	19964	5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid	5326-47-6	C₇H₆INO₂	详情	详情
(II)	28824	2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid	2942-59-8	C₆H₄ClNO₂	详情	详情
(III)	42991	2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid		C₁₃H₉IN₂O₃	详情	详情
(IV)	14881	N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine	108-00-9	C₄H₁₂N₂	详情	详情
(V)	42992	N-[2-(dimethylamino)ethyl]-2-iodo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxamide		C₁₇H₁₉IN₄O₂	详情	详情
(VI)	13265	3-Bromopyridine	626-55-1	C₅H₄BrN	详情	详情
(VII)	38825	3-pyridinylboronic acid	1692-25-7	C₅H₆BNO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IX)

Treatment of 4-bromophthalic anhydride (I) in MeOH with NaOMe affords methyl ester (II), which is then treated with diphenylphosphoryl azide ((PhO)2PON3) in toluene, acetone/H2O to yield a mixture of regioisomers from which derivative (III) is obtained by chromatographic separation. Condensation of (III) with 2-chloronicotinic acid (IV) in refluxing EtOH in the presence of HCl yields pyridoquinazoline acid derivative (V), which is then condensed with N,N-dimethylethylenediamine (VI) in CH2Cl2 using BOP as coupling reagent to provide (VII). Reaction of 2-bromopyridine (VIII) in Et2O with n-BuLi and trimethylborate, followed by treatment with EtOH and HOAc, gives 3-pyridinyl boronic acid (IX), which is finally coupled to (VII) in an Na2CO3 solution via a Suzuki coupling catalyzed by Pd(PPh3)4.

参考文献中间体

合成目标

【1】 Kitchen, D.B.; Schow, S.R.; Casscles, W.T. Jr.; Discafani, C.; Trova, M.P.; Lassota, P.; Zhang, N.; Powell, D.W.; Hetero biarylpyridoquinazolinone derivatives as anticancer agents. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 59.
【2】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. EP 0944628; WO 9823617 .
【3】 Trova, M.P.; Zhang, N. (American Cyanamid Co.); Hetero-biaryl-pyridoquinazolinone derivs. as anti-cancer agents. US 5908840 .

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)	43060	5-bromo-2-benzofuran-1,3-dione	86-90-8	C₈H₃BrO₃	详情	详情
(II)	43061	5-bromo-2-(methoxycarbonyl)benzoic acid		C₉H₇BrO₄	详情	详情
(III)	43062	methyl 2-amino-4-bromobenzoate	135484-83-2	C₈H₈BrNO₂	详情	详情
(IV)	28824	2-Chloropyridine-3-carboxylic acid; 2-Chloronicotinic acid	2942-59-8	C₆H₄ClNO₂	详情	详情
(V)	43063	3-bromo-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxylic acid		C₁₃H₉BrN₂O₃	详情	详情
(VI)	14881	N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine	108-00-9	C₄H₁₂N₂	详情	详情
(VII)	43064	3-bromo-N-[2-(dimethylamino)ethyl]-11-oxo-5,11-dihydro-10lambda(5)-pyrido[2,1-b]quinazoline-6-carboxamide		C₁₇H₁₉BrN₄O₂	详情	详情
(VIII)	13265	3-Bromopyridine	626-55-1	C₅H₄BrN	详情	详情
(IX)	38825	3-pyridinylboronic acid	1692-25-7	C₅H₆BNO₂	详情	详情

Extended Information