4-iodopyrazole;4-Iodo-1H-pyrazole -Drug Synthesis Database

【结构式】

【分子编号】69178

【品名】4-iodopyrazole;4-Iodo-1H-pyrazole

【CA登记号】3469-69-0

【分子式】C₃H₃IN₂

【分子量】193.97

【元素组成】C 18.58% H 1.56% I 65.42% N 14.44%

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：(XIIIa)

Intermediate (III) is prepared by protection of either 4-iodopyrazole (XIIIa) or 4-bromopyrazole (XIIIb) with ethyl vinyl ether (XIV) by means of HCl in toluene or CH2Cl2 to give the corresponding (1-ethoxyethyl)pyrazoles (XVa) and (XVb). Finally, pyrazole (XVa) is submitted to metal-halogen exchange by means of i-PrMgCl in THF, followed by condensation with isopropyl pinacol borate (XVI) (obtained by reaction of pinacol [XVII] with triisopropyl borate at reflux), or pyrazole (XVb) is condensed with methyl pinacol borate (XVIII) by means of i-PrMgCl·LiCl in THF .

参考文献中间体

合成目标

【1】 Lin, Q., Meloni, D., Pan, Y. et al. Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction. Org Lett 2009, 11(9): 1999-2002.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIIa)	69178	4-iodopyrazole;4-Iodo-1H-pyrazole	3469-69-0	C₃H₃IN₂	详情	详情
(XIIIb)	69179			C₃H₃BrN₂	详情	详情
(XVa)	69180	1-(1-ethoxyethyl)-4-iodo-1H-pyrazole		C₇H₁₁IN₂O	详情	详情
(XVb)	69181	4-bromo-1-(1-ethoxyethyl)-1H-pyrazole		C₇H₁₁BrN₂O	详情	详情
(III)	68071	1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole		C₁₃H₂₃BN₂O₃	详情	详情
(XIV)	18762	1-Ethoxyethylene; Ethyl vinyl ether；Ethoxyethene	109-92-2	C₄H₈O	详情	详情
(XVI)	67808	Isopropyl pinacolyl borate;Isopropoxyboronic acid pinacol ester;2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane	61676-62-8	C₉H₁₉BO₃	详情	详情
(XVII)	68108	2,3-Dimethyl-2,3-butanediol;2,3-Dimethylbutane-2,3-diol;Tetramethylethylene glycol;pinacol	76-09-5	C₆H₁₄O₂	详情	详情
(XVIII)	69182	Methoxyboronic acid pinacol ester;2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane	1195-66-0	C₇H₁₅BO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIIIa)

Intermediates (X) and (XII) are prepared by Wittig olefination of cyclopentylcarboxaldehyde (VII) with (triphenylphosphoranylidene)-acetaldehyde (XIX) in benzene at 80 °C, followed by preparative HPLC separation to yield (E)-3-cyclopentylacrylaldehyde (X), which upon asymmetric aza-Michael reaction with 4-bromopyrazole (XIIIa) by means of a chiral catalyst and p-NBA in THF/H2O gives the Michael adduct (XX). Then, aldehyde (XX) is treated with NH4OH and I2 in 1,4-dioxane/H2O to give nitrile (XXI), which is finally reacted with bis(pinacolato)diboron (XXII) in the presence of Pd(PPh3)4 and KOAc in 1,4-dioxane at 120 °C .

参考文献中间体

合成目标

【1】 Lin, Q., Meloni, D., Pan, Y. et al. Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction. Org Lett 2009, 11(9): 1999-2002.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIIa)	69178	4-iodopyrazole;4-Iodo-1H-pyrazole	3469-69-0	C₃H₃IN₂	详情	详情
(B)	69184	2-(bis(3,5-bis(trifluoromethyl)phenyl)((tert-butyldimethylsilyl)oxy)methyl)pyrrolidine		C₂₇H₂₉F₁₂NOSi	详情	详情
(VII)	69171	cyclopentylcarboxaldehyde；Cyclopentanecarbaldehyde;Cyclopentanealdehyde;Cyclopentyl aldehyde;Cyclopentylformaldehyde;Formylcyclopentane	872-53-7	C₆H₁₀O	详情	详情
(X)	69176	(E)-3-cyclopentylacrylaldehyde		C₈H₁₂O	详情	详情
(XII)	69177	(S)-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile		C₁₇H₂₆BN₃O₂	详情	详情
(XIX)	69183	Triphenyl phosphine;Triphenyl phosphorous;(triphenylphosphoranylidene)-acetaldehyde	2136-75-6	C₁₈H₁₅PO	详情	详情
(XX)	69185	(R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanal		C₁₁H₁₅BrN₂O	详情	详情
(XXI)	69186	(R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile		C₁₁H₁₄BrN₃	详情	详情
(XXII)	53342	4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi-1,3,2-dioxaborolane; Bis(pinacolato)diboron; Diboron pinacol ester	73183-34-3	C₁₂H₂₄B₂O₄	详情	详情

Extended Information