2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetonitrile -Drug Synthesis Database

【结构式】

【分子编号】44076

【品名】2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetonitrile

【CA登记号】

【分子式】C₁₅H₁₃ClN₂S

【分子量】288.8004

【元素组成】C 62.38% H 4.54% Cl 12.28% N 9.7% S 11.1%

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：(X)

The reaction of [benzene-U-13C]benzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with the ethanolamine (III) to yield the oxazoline (IV).The chlorination of (IV) with sec-BuLi and hexachloroethane in toluene affords the 2-chlorophenyl derivative (V), which is methylated with MeI to provide the oxazolinium salt (VI). The reduction of (VI) with NaBH4 in ethanol yields the oxazolidine (VII), which is hydrolyzed with HCl to afford the labeled 2-chlorobenzaldehyde (VIII). The condensation of aldehyde (VIII) with the tetrahydrothienopyridine (IX) by means of acetone cyanohydrine in hot toluene affords the substituted acetonitrile (X), which is hydrolyzed to the substituted acetamide (XI) with HCl in methanol. Finally, this compound is treated with H2SO4 in refluxing methanol to afford the target labeled methyl ester as a racemic mixture.

参考文献中间体

合成目标

【1】 Kashimura, S.; Kuwata, F.; Ishige, O.; Uyama, H.; Shono, T.; Yamaguchi, Y.; Formation of a novel acyl anion equivalent by the electroreduction of oxazolinium salts. Chem Lett 1987, 1511.
【2】 Burgos, A.; Simpson, I.; Herbert, J.M.; Ortho-metalation/chlorination of benzoic acid derivatives: Preparation of [benzene-U-C-13]-rac-clopidogrel ([benzene-U-C-13]-rac-SR25990C). J Label Compd Radiopharm 2000, 43, 9, 891.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63476	methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate		C₁₆H₁₆ClNO₂S	详情	详情
	63477	methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate		C₁₆H₁₆ClNO₂S	详情	详情
(I)	10202	Benzoic acid	65-85-0	C₇H₆O₂	详情	详情
(I)	44623			C₇H₆O₂	详情	详情
(II)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(II)	45137			C₇H₅ClO	详情	详情
(III)	21513	2-amino-2-methyl-1-propanol；Karl Fischer;2-Amino-2-methyl-propan-1-ol；2-amino-2-methyl-1-propanol	124-68-5	C₄H₁₁NO	详情	详情
(IV)	44072	4,4-dimethyl-2-phenyl-4,5-dihydro-1,3-oxazole	19312-06-2	C₁₁H₁₃NO	详情	详情
(IV)	45138			C₁₁H₁₃NO	详情	详情
(V)	44073	2-(2-chlorophenyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole		C₁₁H₁₂ClNO	详情	详情
(V)	45139			C₁₁H₁₂ClNO	详情	详情
(VI)	44074	2-(2-chlorophenyl)-3,4,4-trimethyl-4,5-dihydro-1,3-oxazol-3-ium iodide		C₁₂H₁₅ClINO	详情	详情
(VI)	45140			C₁₂H₁₅ClINO	详情	详情
(VII)	44075	2-(2-chlorophenyl)-3,4,4-trimethyl-1,3-oxazolidine		C₁₂H₁₆ClNO	详情	详情
(VII)	45141			C₁₂H₁₆ClNO	详情	详情
(VIII)	24114	2-chlorobenzaldehyde	89-98-5	C₇H₅ClO	详情	详情
(VIII)	45142			C₇H₅ClO	详情	详情
(IX)	34011	4,5,6,7-tetrahydrothieno[3,2-c]pyridine	54903-50-3	C₇H₉NS	详情	详情
(X)	44076	2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetonitrile		C₁₅H₁₃ClN₂S	详情	详情
(X)	45143			C₁₅H₁₃ClN₂S	详情	详情
(XI)	44077	2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetamide		C₁₅H₁₅ClN₂OS	详情	详情
(XI)	45144			C₁₅H₁₅ClN₂OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The condensation of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (I) with 2-chlorobenzaldehyde (II) by means of either KCN/HCl, KCN/AcOH, NaHSO3/KCN, NaHSO3 /NaCN, NaHSO3/Tms-CN, NaCN/HCl or AcOH/cyclo[(S)-His-(S)-Phe] and HCN purge gives 2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetonitrile (III), which is hydrolyzed to the corresponding acetamide (IV) by means of either KOH, NaOH, NaOH followed by H2O2, refluxing HCl/TFA, formic acid/HCl, refluxing HBr, refluxing H2SO4 or refluxing HClO4. Finally, compound (III) is converted into the corresponding methyl ester with MeOH and either dimethylformamide dimethylacetal, H2SO4, Ms-OH, PPA, TiCl4, POCl3 or HCl.

参考文献中间体

合成目标

【1】 Lohray, V.B.; Lohray, B.B.; Pandey, B. (Zydus-Cadila Group); Process for preparing clopidogrel. WO 02059128 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63476	methyl 2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate		C₁₆H₁₆ClNO₂S	详情	详情
(I)	34011	4,5,6,7-tetrahydrothieno[3,2-c]pyridine	54903-50-3	C₇H₉NS	详情	详情
(II)	24114	2-chlorobenzaldehyde	89-98-5	C₇H₅ClO	详情	详情
(III)	44076	2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetonitrile		C₁₅H₁₃ClN₂S	详情	详情
(IV)	44077	2-(2-chlorophenyl)-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetamide		C₁₅H₁₅ClN₂OS	详情	详情

Extended Information