2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine -Drug Synthesis Database

【结构式】

【分子编号】43460

【品名】2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine

【CA登记号】1141-88-4

【分子式】C₁₂H₁₂N₂S₂

【分子量】248.37276

【元素组成】C 58.03% H 4.87% N 11.28% S 25.82%

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：(V)

Cyclohexanecarboxylic acid (I) is condensed with 1-bromo-2-ethylbutane (II) by means of lithium diisopropylamide (LDA) (NaH can also be added ) in THF or THF/cyclohexane to afford derivative (III). Treatment of carboxylic acid (III) with oxalyl chloride in CH2Cl2 (a small amount of DMF can be added) yields acid chloride (IV), which is then coupled with bis(2-aminophenyl) disulfide (V) in pyridine to provide disulfide derivative (VI). Reduction of the disulfide bond of (VI) with PPh3 in dioxane/H2O gives benzenethiol (VII), which is finally coupled with isobutyryl chloride (VIII) in pyridine/CHCl3 to furnish the target compound.

参考文献中间体

合成目标

【2】 Maeda, K.; Okamoto, H.; Shinkai, H. (Japan Tobacco Inc.); CEPT activity inhibitors. EP 1020439; JP 1999049743; JP 1999222428; WO 9835937 .
【1】 maeda, K.; Shinkai, H.; Yamasaki, T.; Okamoto, H.; Uchida, I.; Bis(2-(acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J Med Chem 2000, 43, 19, 3566.

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)	44803	cyclohexanecarboxylic acid	98-89-5	C₇H₁₂O₂	详情	详情
(II)	44804	1-(1-ethylpropyl)-1lambda(3)-dibromane		C₅H₁₂Br₂	详情	详情
(III)	44805	1-(2-ethylbutyl)cyclohexanecarboxylic acid		C₁₃H₂₄O₂	详情	详情
(IV)	44806	1-(2-ethylbutyl)cyclohexanecarbonyl chloride		C₁₃H₂₃ClO	详情	详情
(V)	43460	2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine	1141-88-4	C₁₂H₁₂N₂S₂	详情	详情
(VI)	44807	1-(2-ethylbutyl)-N-(2-[[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]disulfanyl]phenyl)cyclohexanecarboxamide		C₃₈H₅₆N₂O₂S₂	详情	详情
(VII)	44808	1-(2-ethylbutyl)-N-(2-sulfanylphenyl)cyclohexanecarboxamide		C₁₉H₂₉NOS	详情	详情
(VIII)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Amine intermediate (XIV) has been obtained as follows: N-(Carbobenzoxy)-L-aspartic acid alpha-benzyl ester (VII) was converted to acid chloride (VIII) and then coupled to 2-aminophenyl disulfide (IX) to afford the bis-amide (X). Reductive cleavage of the disulfide group of (X), followed by basic cyclization, produced the benzothiazole (XI) (2). Hydrolysis of the benzyl ester group of (XI) and subsequent coupling of the resulting carboxylic acid (XII) with piperidine (VI) gave amide (XIII). The carbobenzoxy group of (XII) was then cleaved with HBr in HOAc, yielding intermediate amine (XIV).

参考文献中间体

合成目标

【1】 Baettig, U.; et al.; The design and synthesis of thrombin inhibitors: Analogues of MD805 containing non-polar surrogates for arginine at the P1 position. Bioorg Med Chem Lett 2000, 10, 14, 1563.
【2】 Smith, G.P.; Brundish, D.E.; Menear, K.A.; Walker, C.V.; Herold, P.; Fullerton, J.D.; Allen, M.C.; Le Grand, D.M.; Kane, P.D.; Cockcroft, X.-L.; Wathey, W.B.; Butler, P.I.; Hatto, J.D.I.; Hayler, J.D. (Novartis AG); Tetrahydroquinoline inhibitors of trypsin and thrombin. GB 2312674 .

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)	28517	4-(2-fluoroethyl)piperidine		C₇H₁₄FN	详情	详情
(VII)	43458	(3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutyric acid	4779-31-1	C₁₉H₁₉NO₆	详情	详情
(VIII)	43459	benzyl (2S)-2-[[(benzyloxy)carbonyl]amino]-4-chloro-4-oxobutanoate		C₁₉H₁₈ClNO₅	详情	详情
(IX)	43460	2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine	1141-88-4	C₁₂H₁₂N₂S₂	详情	详情
(X)	43461	benzyl (2S)-4-[2-([2-[((3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutanoyl)amino]phenyl]disulfanyl)anilino]-2-[[(benzyloxy)carbonyl]amino]-4-oxobutanoate		C₅₀H₄₆N₄O₁₀S₂	详情	详情
(XI)	43462	benzyl (2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propanoate		C₂₅H₂₂N₂O₄S	详情	详情
(XII)	43463	(2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propionic acid		C₁₈H₁₆N₂O₄S	详情	详情
(XIII)	43464	benzyl (1S)-1-(1,3-benzothiazol-2-ylmethyl)-2-[4-(2-fluoroethyl)-1-piperidinyl]-2-oxoethylcarbamate		C₂₅H₂₈FN₃O₃S	详情	详情
(XIV)	43465	(2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone		C₁₇H₂₂FN₃OS	详情	详情

Extended Information