2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】15825

【品名】2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]acetic acid

【CA登记号】

【分子式】C₂₃H₂₃NO₃

【分子量】361.44056

【元素组成】C 76.43% H 6.41% N 3.88% O 13.28%

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：(IV)

The racemic mixture containing the (R)-enantiomer BAY X 1005 (IV) can be prepared according to the following scheme: 4-Hydroxyphenylacetic acid methyl ester (I) is coupled with 2-chloromethylquinoline and potassium carbonate in DMF. The resulting product (II) is alkylated with cyclopentylbromide and sodium hydride in DMF to give product (III). Final saponification is undertaken with sodium hydroxide in methanol leading to the racemic carboxylic acid (IV).

参考文献中间体

合成目标

【1】 Muller-Peddinghaus, R.; Raddatz, S.; BAY X 1005. Drugs Fut 1995, 20, 10, 996.
【2】 Mohrs, K.; Raddatz, S.; Perzborn, E.; Fruchtmann, R.; Kohlsdorfer, C.; Müller-Peddinghaus, R.; Theisen, P. (Bayer AG); Substd. 4-(quinoline-2-yl-methoxy)phenyl-acetic acid derivs. AU 8935270; DE 3900261; EP 0344519; JP 1990019359; JP 1998053577; US 4970215 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10972	1-Bromocyclopentane; Cyclopentyl bromide	137-43-9	C₅H₉Br	详情	详情
	13162	2-(Chloromethyl)quinoline; alpha-Chloroquinaldine	4377-41-7	C₁₀H₈ClN	详情	详情
(I)	15822	Methyl 4-hydroxyphenylacetate; methyl 2-(4-hydroxyphenyl)acetate	14199-15-6	C₉H₁₀O₃	详情	详情
(II)	15823	methyl 2-[4-(2-quinolinylmethoxy)phenyl]acetate		C₁₉H₁₇NO₃	详情	详情
(III)	15824	methyl 2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]acetate		C₂₄H₂₅NO₃	详情	详情
(IV)	15825	2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]acetic acid		C₂₃H₂₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Separation of the Enantiomer: The enantiomers are separated from the racemic carboxylic acid (IV). After activation of the carboxylic acid group as imidazolide (V), this compound reacts with L-phenylglycinol and toluene sulfonic acid in DMF forming the diastereomeric mixture of L-phenylglycinolamides. These diastereomers can be separated by fractionated crystallization using ethanol (diastereomer VI) or a mixture of diethylether and isopropanol (diastereomer VII) as solvents. The release of enantiomerically pure carboxylic acids (VIII) and (IX) takes place by cleavage of the amide bond with sulfuric acid, neutralization and recrystallization from ethanol. The (R)-(-)-enantiomer is the active leukotriene synthesis inhibitor BAY X 1005.

参考文献中间体

合成目标

【1】 Muller-Peddinghaus, R.; Raddatz, S.; BAY X 1005. Drugs Fut 1995, 20, 10, 996.
【2】 Mohrs, K.; Raddatz, S.; Perzborn, E.; Fruchtmann, R.; Kohlsdorfer, C.; Müller-Peddinghaus, R.; Theisen, P. (Bayer AG); Substd. 4-(quinoline-2-yl-methoxy)phenyl-acetic acid derivs. AU 8935270; DE 3900261; EP 0344519; JP 1990019359; JP 1998053577; US 4970215 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10973	(2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol	20989-17-7	C₈H₁₁NO	详情	详情
	11353	1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole)	530-62-1	C₇H₆N₄O	详情	详情
(IV)	15825	2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]acetic acid		C₂₃H₂₃NO₃	详情	详情
(V)	15826	2-cyclopentyl-1-(1H-imidazol-1-yl)-2-[4-(2-quinolinylmethoxy)phenyl]-1-ethanone		C₂₆H₂₅N₃O₂	详情	详情
(VI)	15827	(2S)-2-cyclopentyl-N-[(1S)-2-hydroxy-1-phenylethyl]-2-[4-(2-quinolinylmethoxy)phenyl]ethanamide		C₃₁H₃₂N₂O₃	详情	详情
(VII)	15828	(2R)-2-cyclopentyl-N-[(1S)-2-hydroxy-1-phenylethyl]-2-[4-(2-quinolinylmethoxy)phenyl]ethanamide		C₃₁H₃₂N₂O₃	详情	详情
(VIII)	15829	(2S)-2-cyclopentyl-2-[4-(2-quinolinylmethoxy)phenyl]ethanoic acid		C₂₃H₂₃NO₃	详情	详情

Extended Information