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【结 构 式】

【分子编号】38833

【品名】5-bromo-6-chloro-3-pyridinol

【CA登记号】

【 分 子 式 】C5H3BrClNO

【 分 子 量 】208.44166

【元素组成】C 28.81% H 1.45% Br 38.33% Cl 17.01% N 6.72% O 7.68%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

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.

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:(II)

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.

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
Extended Information