4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】50284

【品名】4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride

【CA登记号】

【分子式】C₁₂H₁₆ClNO₄S

【分子量】305.78208

【元素组成】C 47.14% H 5.27% Cl 11.59% N 4.58% O 20.93% S 10.49%

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：(XVI)

Intermediate benzamide (XVI): The sulfonation of 3-hydroxybenzoic acid (XII) with SO3/H2SO4 gives 3-hydroxy-4-sulfobenzoic acid (XIII), which is methylated by means of Me2SO4 and KOH to yield the methoxybenzoic acid (XIV). The reaction of (XIV) with PCl5 affords the dichloride (XV), which is finally treated with tert-butylamine and TEA to provide the target benzamide intermediate (XVI).

参考文献中间体

合成目标

【1】 Venkatesan, H.; et al.; Total synthesis of SR 121463 A, a highly potent and selective vasopressin V2 receptor antagonist. J Org Chem 2001, 66, 11, 3653.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	50280	3-Hydroxybenzoic acid	99-06-9	C₇H₆O₃	详情	详情
(XIII)	50281	3-hydroxy-4-sulfobenzoic acid		C₇H₆O₆S	详情	详情
(XIV)	50282	potassium 4-carboxy-2-methoxybenzenesulfonate		C₈H₇KO₆S	详情	详情
(XV)	50283	4-(chlorosulfonyl)-3-methoxybenzoyl chloride		C₈H₆Cl₂O₄S	详情	详情
(XVI)	50284	4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride		C₁₂H₁₆ClNO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Assembly of the target compound: The reaction of methyl 3-bromopropionate (XVII) with ethylmagnesium bromide (XVIII) and Ti(iPrO)4 gives 1-(2-bromoethyl)cyclopropan-1-ol (XIX), which is brominated by NBS in CCl4 to yield 1,5-dibromo-3-pentanone (XX). The reaction of (XX) with ethylene glycol (XXI), HC(OEt)3 and PPTS affords the cyclic ketal (XXII), which is cyclized with the indolinone intermediate (VII) by means of NaH in DMF to provide the spiro compound (XXIII). The deprotection of (XXIII) with PPTS in acetone/water gives the spiranic diketone (XXIV), which is selectively reduced with NaBH4 in methanol to yield the spiro cyclohexanol (XXV). The condensation of (XXV) with 4-(2-chloroethyl)morpholine (XXVI) by means of NaH in hot toluene affords the corresponding ether (XXVII), which is debenzylated by means of Li/NH3 to provide intermediate (XXVIII) with a free NH group. Finally, the sulfonation of (XXVIII) with intermediate chlorosulfonyl benzamide (XVI) by means of potassium tert-butoxide gives the target sulfonyl benzamide compound.

参考文献中间体

合成目标

【1】 Venkatesan, H.; et al.; Total synthesis of SR 121463 A, a highly potent and selective vasopressin V2 receptor antagonist. J Org Chem 2001, 66, 11, 3653.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	50276	1-benzyl-5-ethoxy-1,3-dihydro-2H-indol-2-one		C₁₇H₁₇NO₂	详情	详情
(XVI)	50284	4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride		C₁₂H₁₆ClNO₄S	详情	详情
(XVII)	50285	3-Bromopropionic acid methyl ester; Methyl 3-bromopropionate	3395-91-3	C₄H₇BrO₂	详情	详情
(XVIII)	24239	bromo(ethyl)magnesium；ethylmagnesium bromide	925-90-6	C₂H₅BrMg	详情	详情
(XIX)	50286	1-(2-bromoethyl)cyclopropanol		C₅H₉BrO	详情	详情
(XX)	50287	1,5-dibromo-3-pentanone		C₅H₈Br₂O	详情	详情
(XXI)	11295	Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol	107-21-1	C₂H₆O₂	详情	详情
(XXII)	50288	2,2-bis(2-bromoethyl)-1,3-dioxolane		C₇H₁₂Br₂O₂	详情	详情
(XXIII)	50289			C₂₄H₂₇NO₄	详情	详情
(XXIV)	50290			C₂₂H₂₃NO₃	详情	详情
(XXV)	50291			C₂₂H₂₅NO₃	详情	详情
(XXVI)	27355	4-(2-chloroethyl)morpholine	3647-69-6	C₆H₁₂ClNO	详情	详情
(XXVII)	50292			C₂₈H₃₆N₂O₄	详情	详情
(XXVIII)	50293			C₂₁H₃₀N₂O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

The reduction of diethyl 3-(methoxymethoxy)glutarate (I) with LiAlH4 in THF gives 3-(methoxymethoxy)pentane-1,5-diol (II), which is treated with Ts-OH and TEA in THF to yield the disulfonate (III). The condensation of (III) with 5-ethoxyindolin-2-one (IV) by means of tBu-OK in THF affords the spiro compound (V), which is deprotected with HCl in methanol to afford the spiranic alcohol (VI). The oxidation of (VI) with pyridinium chlorochromate (PCC) over Al2O3 provides the spiranic cyclohexanone (VII), which is treated with 2-chloroethanol (VIII) and Ms-OH in toluene to give the ketal (IX). The reaction of (IX) with zinc borohydride and trimethylsilyl chloride in ethyl ether/dichloromethane yields the 2-chloroethoxy derivative (X), which is condensed with 4-(N-tert-butylcarbamoyl)-2-methoxybenzenesulfonyl chloride (XI) by means of tBu-OK in THF to afford the adduct (XII). Finally, the target compound is obtained by condensation of (XII) with morpholine (XIII) by means of NaI in DMF, followed by treatment with fumaric acid.

参考文献中间体

合成目标

【1】 Di Malta, A.; Foulon, L.; Garcia, G.; Nisato, D.; Roux, R.; Serradeil-Legal, C.; Valette, G.; Wagnon, J. (Sanofi-Synthélabo); Derivs. of 1-benzenesulfonyl-1,3-dihydro-indol-2-one, their preparation and pharmaceutical compsns. containing them. CA 2129215; EP 0636608; FR 2708605; JP 1995247269 .
【2】 Foulon, L.; Garcia, G.; Serradeil-Le Gal, C.; Valette, G. (Sanofi-Synthelabo); 3-Spiro-indolin-2-one derivs. as vasopressin and/or oxytocin receptor ligands. EP 0873309; FR 2740136; JP 1999509232; JP 2001302631; US 5994350; WO 9715556 .

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)	50294	diethyl 3-(methoxymethoxy)pentanedioate		C₁₁H₂₀O₆	详情	详情
(II)	50295	3-(methoxymethoxy)-1,5-pentanediol		C₇H₁₆O₄	详情	详情
(III)	50296	3-(methoxymethoxy)-5-[[(4-methylphenyl)sulfonyl]oxy]pentyl 4-methylbenzenesulfonate		C₂₁H₂₈O₈S₂	详情	详情
(IV)	50297	5-ethoxy-1,3-dihydro-2H-indol-2-one		C₁₀H₁₁NO₂	详情	详情
(V)	50298			C₁₇H₂₃NO₄	详情	详情
(VI)	50299			C₁₅H₁₉NO₃	详情	详情
(VII)	50300			C₁₅H₁₇NO₃	详情	详情
(VIII)	10384	2-Chloro-1-ethanol; Ethylene chlorohydrin	107-07-3	C₂H₅ClO	详情	详情
(IX)	50301			C₁₉H₂₅Cl₂NO₄	详情	详情
(X)	50302			C₁₇H₂₂ClNO₃	详情	详情
(XI)	50284	4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride		C₁₂H₁₆ClNO₄S	详情	详情
(XII)	50303			C₂₉H₃₇ClN₂O₇S	详情	详情
(XIII)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情

Extended Information