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【结 构 式】

【分子编号】50173

【品名】5-fluoro-2-iodoaniline; 5-fluoro-2-iodophenylamine

【CA登记号】

【 分 子 式 】C6H5FIN

【 分 子 量 】237.0153132

【元素组成】C 30.41% H 2.13% F 8.02% I 53.54% N 5.91%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(I)

Condensation between 2-iodo-5-fluoroaniline (I) and phenylacetylene (II) under catalysis with Pd(PPh3)4, CuI and diethylamine, followed by cyclization catalyzed by CuI and CaCO3 in DMF, affords phenylindole (III), which is then coupled with 4-piperidone (IV) in H3PO4/HOAc to provide tetrahydropyridine derivative (V). Protection of (V) as its benzyloxycarbonyl derivative (VII) by reaction with acid chloride (VI), followed by hydroboration with bis-isopinocampheylborane ((-)-Ipc2BH) and H2O2 in NaOH, provides the secondary alcohol (VIII). Isolation of enantiomer (IX) is then performed by reaction of (VIII) with the acid chloride derived from (1R)-(+)-camphanic acid, separation of diastereoisomers by chromatography and hydrolysis with K2CO3 in MeOH. Treatment of (IX) with diethylaminosulfur trifluoride (DAST) in EtOAc induces a regiospecific and enantioselective rearrangement affording 3-(3-indolyl)-4-fluoropiperidine (X), which is finally converted into the desired compound by deprotection with formic acid and Pd/C.

1 Rowley, M.; et al.; 3-(4-Fluoropiperidin-3-yl)-2-phenylindoles as high affinity, selective, and orally bioavailable h5-HT2A receptor antagonists. J Med Chem 2001, 44, 10, 1603.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
50178 7,7-dimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride C9H11ClO3 详情 详情
(I) 50173 5-fluoro-2-iodoaniline; 5-fluoro-2-iodophenylamine C6H5FIN 详情 详情
(II) 20597 1-ethynylbenzene 536-74-3 C8H6 详情 详情
(III) 50174 6-fluoro-2-phenyl-1H-indole C14H10FN 详情 详情
(IV) 27115 4-piperidinone 40064-34-4 C5H9NO 详情 详情
(V) 50175 6-fluoro-2-phenyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole C19H17FN2 详情 详情
(VI) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(VII) 50176 benzyl 4-[2-(1,2,3,5-cyclohexatetraen-1-yl)-6-fluoro-1H-indol-3-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate C27H21FN2O2 详情 详情
(VIII) 50177 benzyl 4-(6-fluoro-2-phenyl-1H-indol-3-yl)-3-hydroxy-1-piperidinecarboxylate C27H25FN2O3 详情 详情
(IX) 50179 benzyl (3S,4S)-4-(6-fluoro-2-phenyl-1H-indol-3-yl)-3-hydroxy-1-piperidinecarboxylate C27H25FN2O3 详情 详情
(X) 50180 benzyl (3R,4R)-4-fluoro-3-(6-fluoro-2-phenyl-1H-indol-3-yl)-1-piperidinecarboxylate C27H24F2N2O2 详情 详情
Extended Information