5-Chloro-2-oxo-1-indolinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】14096

【品名】5-Chloro-2-oxo-1-indolinecarboxamide

【CA登记号】

【分子式】C₉H₇ClN₂O₂

【分子量】210.61956

【元素组成】C 51.32% H 3.35% Cl 16.83% N 13.3% O 15.19%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

A new synthesis of tenidap sodium has been described: The reaction of 4,5-dibromothiophene-2-carboxylic acid (I) with hot SOCl2 gives the corresponding acyl chloride (II), which is condensed with 5-chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (III) by means of 4-(dimethylamino)pyridine (DMAP) in DMF, yielding 5-chloro-3-[(4,5-dibromothien-2-yl)hydroxymethylene]-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (IV). Finally, this compound is debrominated by hydrogenation with H2 over Pd/BaSO4 in methanol.

参考文献中间体

合成目标

【1】 Schulte, G.R.; Ehrgott, F.J. (Pfizer Inc.); 3-Aroyl-2-oxindole-1-carboxamides. EP 0421749; JP 1991151380; US 5059693 .

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)	14094	4,5-Dibromo-2-thiophenecarboxylic acid; 4,5-Dibromothiophene-2-carboxylic acid	7311-68-4	C₅H₂Br₂O₂S	详情	详情
(II)	14095	4,5-Dibromo-2-thiophenecarbonyl chloride		C₅HBr₂ClOS	详情	详情
(III)	14096	5-Chloro-2-oxo-1-indolinecarboxamide		C₉H₇ClN₂O₂	详情	详情
(IV)	14097	5-Chloro-3-[(Z)-(4,5-dibromo-2-thienyl)(hydroxy)methylidene]-2-oxo-1H-indole-1(2H)-carboxamide		C₁₄H₇Br₂ClN₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The synthesis of [14C]-labeled tenidap sodium has been reported: The chlorination of [14C]-2,3-dihydro-1H-indole-2,3-dione (I) with sulfuryl chloride and triethylamine in hot acetonitrile gives the 5-chloro derivative (II), which is partially reduced by treatment with hydrazine hydrate in refluxing ethanol, followed by a treatment with KOH in the same refluxing solvent, to yield 5-chloro-2,3-dihydro-1H-indol-2-one (III). The reaction of (III) with chlorosulfonyl isocyanate (IV) in refluxing dichloromethane affords 5-chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (V), which is condensed with 2-thienylcarbonyl chloride (VI) by means of dimethylaminopyridine (DMAP) and triethylamine (TEA) in DMF, giving tenidap (VII). Finally, this compound is treated with NaHCO3 in hot acetone.

参考文献中间体

合成目标

【1】 Hale, K.J.; Lennon, J.A.; Hobbs, C.J.; Javaid, M.H.; Manaviazar, S.; Asymmetric synthesis of the C17-C27 segment of the antineoplasticmacrolide bryostatin 1. J Label Compd Radiopharm 1995, 36, 8, 1359.
【2】 Johnson, D.L.; Melvin, L.S.; Falkner, F.C.; Rusek, F.W.; Robinson, R.P.; Synthesis of C-14 isotopic isomers of tenidap - A novel antiinflammatory agent. J Label Compd Radiopharm 1996, 38, 3, 207.

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)	14098	2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin	91-56-5	C₈H₅NO₂	详情	详情
(I)	45196			C₈H₅NO₂	详情	详情
(II)	14099	5-Chloro-1H-indole-2,3-dione; 5-Chloroisatin	17630-76-1	C₈H₄ClNO₂	详情	详情
(II)	45197			C₈H₄ClNO₂	详情	详情
(III)	14100	5-Chlorooxindole; 5-Chloro-1,3-dihydro-2H-indol-2-one	17630-75-0	C₈H₆ClNO	详情	详情
(III)	45198			C₈H₆ClNO	详情	详情
(IV)	14101	Chlorosulfonyl isocyanate	1189-71-5	CClNO₃S	详情	详情
(V)	14096	5-Chloro-2-oxo-1-indolinecarboxamide		C₉H₇ClN₂O₂	详情	详情
(V)	45199			C₉H₇ClN₂O₂	详情	详情
(VI)	14103	2-Thiophenecarbonyl chloride	5271-67-0	C₅H₃ClOS	详情	详情
(VII)	14104	5-Chloro-3-[(Z)-hydroxy(2-thienyl)methylidene]-2-oxo-1H-indole-1(2H)-carboxamide		C₁₄H₉ClN₂O₃S	详情	详情
(VII)	45200			C₁₄H₉ClN₂O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

5-Chloro-2-oxo-2,3-dihydro-1H-indole-1-carboxamide (X), a key intermediate in the synthesis of tenidap, has been obtained by several different ways, all of them starting from 5-chloro-2,3-dihydro-1H-indol-2-one (I). 1. The reaction of indolone (I) with cyclohexylcarbonyl isocyanate (II) gives the N-acyl carboxamide (III), which is treated with KOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (IV). Finally, this compound is cyclized to the target carboxamide by treatment with trifluoroacetic anhydride and trifluoroacetic acid. 2. The reaction of indolone (I) with isobutyryl isocyanate (XI) gives the N-acyl carboxamide (V), which is treated with KOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (III). Finally, this compound is cyclized to the target carboxamide as before. 3. The reaction of indolone (I) with trichloroacetyl isocyanate (VI) in hot toluene gives the target carboxamide in one step. 4. The reaction of indolone (I) with chlorosulfonyl isocyanate (VII) gives the N-chlorosulfonyl carboxamide (VIII), which is hydrolyzed to the target carboxamide with aqueous acetic acid. 5. The reaction of indolone (I) with NaOH and then with H2SO4 gives 2-(2-amino-5-chlorophenyl)acetic acid (IX), which is treated with potassium isocyanate and AcOH to yield 2-(5-chloro-2-ureidophenyl)acetic acid (III). Finally, this compound can be cyclized to the target intermediate by means of AcOH and NaOAc.

参考文献中间体

合成目标

【1】 Sarma, M.R.; Goud, P.S.; Sailaja, M.; Kumar, P.R.; Reddy, G.O.; Raju, S.; Synthesis of tenidap: An improved process for the preparation of 5-chloro-2-oxindole-1-carboxamide. Org Process Res Dev 2001, 5, 1, 61.

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)	14100	5-Chlorooxindole; 5-Chloro-1,3-dihydro-2H-indol-2-one	17630-75-0	C₈H₆ClNO	详情	详情
(II)	47903	cyclohexanecarbonyl isocyanate		C₈H₁₁NO₂	详情	详情
(III)	47904	5-chloro-N-(cyclohexylcarbonyl)-2-oxo-1-indolinecarboxamide		C₁₆H₁₇ClN₂O₃	详情	详情
(IV)	47905	2-[2-[(aminocarbonyl)amino]-5-chlorophenyl]acetic acid		C₉H₉ClN₂O₃	详情	详情
(V)	47906	5-chloro-N-isobutyryl-2-oxo-1-indolinecarboxamide		C₁₃H₁₃ClN₂O₃	详情	详情
(VI)	40725	2,2,2-trichloroacetyl isocyanate	3019-71-4	C₃Cl₃NO₂	详情	详情
(VII)	14101	Chlorosulfonyl isocyanate	1189-71-5	CClNO₃S	详情	详情
(VIII)	47907	5-chloro-1-[[(chlorosulfonyl)amino]carbonyl]-2-oxoindoline		C₉H₆Cl₂N₂O₄S	详情	详情
(IX)	47908	2-(2-amino-5-chlorophenyl)acetic acid		C₈H₈ClNO₂	详情	详情
(X)	14096	5-Chloro-2-oxo-1-indolinecarboxamide		C₉H₇ClN₂O₂	详情	详情
(XI)	47909	2-methylpropanoyl isocyanate		C₅H₇NO₂	详情	详情

Extended Information