6-chloro-1,3-dihydro-2H-indol-2-one -Drug Synthesis Database

【结构式】

【分子编号】16275

【品名】6-chloro-1,3-dihydro-2H-indol-2-one

【CA登记号】56341-37-8

【分子式】C₈H₆ClNO

【分子量】167.59448

【元素组成】C 57.33% H 3.61% Cl 21.15% N 8.36% O 9.55%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(II)

Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II), which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III). The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV). 1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII). Finally, intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.

参考文献中间体

合成目标

【1】 Lowe, J.A. III; Nagel, A.A. (Pfizer Inc.); Piperazinyl-heterocyclic cpds. US 4831031 .
【2】 Bowles, P. (Pfizer Inc.); Process for preparing aryl piperazinyl-heterocyclic cpds. EP 1029861; JP 1994184143; US 5206366 .
【3】 Howard, H.R. Jr.; Busch, F.R.; Grobin, A.W.; Leeman, K.R. (Pfizer Products Inc.); Controlled synthesis of ziprasidone and compsns. thereof. WO 0370246 .
【4】 Seeger, T.F.; Prakash, C.; Howard, H.R.; Ziprasidone Hydrochloride. Drugs Fut 1994, 19, 6, 560.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(I)	16274	6-chloro-1H-indole-2,3-dione; 6-Chloroisatin	6341-92-0	C₈H₄ClNO₂	详情	详情
(II)	16275	6-chloro-1,3-dihydro-2H-indol-2-one	56341-37-8	C₈H₆ClNO	详情	详情
(III)	16276	6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one		C₁₀H₇Cl₂NO₂	详情	详情
(IV)	16277	6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one; 5-chloroethyl-6-chloro-1,3-dihydro-1H-indol-2-one-		C₁₀H₉Cl₂NO	详情	详情
(V)	16278	1,2-benzisothiazol-3(2H)-one; 1,2-Benzisothiazolin-3-one	2634-33-5	C₇H₅NOS	详情	详情
(VI)	16279	3-chloro-1,2-benzisothiazole		C₇H₄ClNS	详情	详情
(VII)	16280	3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl)	87691-87-0	C₁₁H₁₃N₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

A new synthesis for ziprasidone hydrochloride has been reported: The condensation of 6-chloroindolin-2-one (I) with bromoacetic acid (II) by means of polyphosphoric acid (PPA) gives 5-(bromoacetyl)-6-chloroindolin-2-one (III), which is reduced with triethylsilane and trifluoroacetic acid to the corresponding 2-bromoethyl derivative (IV). Finally, this compound is condensed with 4-(3-benzisothiazolyl)piperazine (V) by means of Na2CO3 in DMF or isobutyl methyl ketone.

参考文献中间体

合成目标

【1】 Howard, H.R.; Lowe, J.A. III, Seeger, T.F.; et al.; 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem 1996, 39, 1, 143.

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)	16275	6-chloro-1,3-dihydro-2H-indol-2-one	56341-37-8	C₈H₆ClNO	详情	详情
(II)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(III)	16283	5-(2-bromoacetyl)-6-chloro-1,3-dihydro-2H-indol-2-one		C₁₀H₇BrClNO₂	详情	详情
(IV)	16284	5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one		C₁₀H₉BrClNO	详情	详情
(V)	16280	3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl)	87691-87-0	C₁₁H₁₃N₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The Friedel Crafts condensation of 6-chloroindolin-2-one (I) with 14C labeled 2-chloroacetyl chloride (II) by means of AlCl3 in CS2 gives 6-chloro-5-(2-chloroacetyl)indolin-2-one (III), which is reduced with trimethylsilane in TFA to yield the labeled chloroethyl derivative (IV). Finally, this compound is condensed with 3-(1-piperazinyl)-1,2-benzoisothiazole (V) by means of Na2CO3 in refluxing water to provide the target radiolabeled compound.

参考文献中间体

合成目标

【1】 Howard, H.R.; Shenk, K.D.; Smolarek, T.A.; Marx, M.H.; Windels, J.H.; Roth, R.W.; Synthesis of H-3- and C-14-labelled CP-88,059: A potent atypical antipsychotic agent. J Label Compd Radiopharm 1994, 34, 2, 117.

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)	16275	6-chloro-1,3-dihydro-2H-indol-2-one	56341-37-8	C₈H₆ClNO	详情	详情
(II)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(II)	62883	2-chloroacetyl chloride		C₂Cl₂O	详情	详情
(III)	16276	6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one		C₁₀H₇Cl₂NO₂	详情	详情
(III)	62884	6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one		C₁₀H₅Cl₂NO₂	详情	详情
(IV)	16277	6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one; 5-chloroethyl-6-chloro-1,3-dihydro-1H-indol-2-one-		C₁₀H₉Cl₂NO	详情	详情
(IV)	62885	6-Chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one		C₁₀H₇Cl₂NO	详情	详情
(V)	16280	3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl)	87691-87-0	C₁₁H₁₃N₃S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Venkataraman S, RAO UVB, Muwa V, et al. 2006. Process for the preparation of highly pure zipnsidone hydrochloride. US 2006089502

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（VI）	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(I)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(II)	16275	6-chloro-1,3-dihydro-2H-indol-2-one	56341-37-8	C₈H₆ClNO	详情	详情
(III)	16276	6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one		C₁₀H₇Cl₂NO₂	详情	详情
(IV)	16277	6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one; 5-chloroethyl-6-chloro-1,3-dihydro-1H-indol-2-one-		C₁₀H₉Cl₂NO	详情	详情
(V)	16280	3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl)	87691-87-0	C₁₁H₁₃N₃S	详情	详情

合成路线5

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Howard HR, Shenk KD, Smolarek TA, et aL. 1994. Synthesis of ³H-and ¹⁴C-labeled CP-88 059: a potent atypical antipsychotic agent. J Label Comp Radiopharm, 34 (2), 117～125

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	66979	6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one; 5-chloroethyl-6-chloro-1,3-dihydro-1H-indol-2-one-		C₉¹⁴CH₉Cl₂NO	详情	详情
(VII)	16280	3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl)	87691-87-0	C₁₁H₁₃N₃S	详情	详情
(I)	66976	2-chloroacetic acid		C¹⁴CH₃ClO₂	详情	详情
(II)	23811	phthaloyl dichloride;1,2-Benzenedicarbonyl dichloride;o-Phthaloyl chloride	88-95-9	C₈H₄Cl₂O₂	详情	详情
(III)	66977	2-chloroacetyl chloride;Chloroacetylchloride;Monochloroacetyl chloride		C¹⁴CH₂Cl₂O	详情	详情
(IV)	16275	6-chloro-1,3-dihydro-2H-indol-2-one	56341-37-8	C₈H₆ClNO	详情	详情
(V)	66978	6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one		C₉¹⁴CH₇Cl₂NO₂	详情	详情

Extended Information