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【结 构 式】 
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【分子编号】39041 【品名】butylamine; 1-butanamine 【CA登记号】109-73-9 |
【 分 子 式 】C4H11N 【 分 子 量 】73.13808 【元素组成】C 65.69% H 15.16% N 19.15% |
合成路线1
该中间体在本合成路线中的序号：(A)Anthranitic acid (I) is reacted with cyclohexanone (II) to give 5-hydroxy-1,2,3,4-tetrahydroacridine (III). The hydroxy compound (III) is then reacted with phosphorous oxychloride to give 5-chloro-1,2,3,4-tetrahydroacridine (IV). Aminolysis of (IV) with n-butylamine affords centbucridine.
| 【1】 Arya, V.P.; Centbucridine. Drugs Fut 1980, 5, 6, 281. |
| 【2】 Patnaik, G.K.; et al.; Studies in 4-substituted 2,3-polymethylene quinolines. CNS Drugs Ed. G.S. Sidhu, CSI, New Delhi . |
| 【3】 Patnaik, G.K.; et al.; Compounds acting on the central nervous system. IV. 4-substituted 2,3-polymethylenequinolines. J Med Chem 1966, 9, 4, 483. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 39041 | butylamine; 1-butanamine | 109-73-9 | C4H11N | 详情 | 详情 |
| (I) | 11661 | 2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid | 118-92-3 | C7H7NO2 | 详情 | 详情 |
| (II) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (III) | 39040 | 1,2,3,4-tetrahydro-9-acridinol | C13H13NO | 详情 | 详情 | |
| (IV) | 28181 | 9-chloro-1,2,3,4-tetrahydroacridine | C13H12ClN | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Reaction of 4-ethynylanisole (I) with nido-decaborane (II) in acetonitrile/benzene affords compound (III), which is then converted into (V) by reaction with BuLi in DME followed by treatment with CuCl and condensation with 2-(11-bromo-n-undecyloxy)tetrahydro-2H-pyran (IV) in pyridine. Removal of the THP group with p-toluenesulfonic acid in MeOH gives alcohol (VI), which is oxidized with CrO3 and H2SO4 in acetone to provide carboxylic acid (VIII) and ester (VII). Ester (VII) is then converted into carboxylic acid (VIII) by hydrolysis with H2SO4 in dioxane/H2O, which is demethylated with BBr3 in CH2Cl2. Finally, the resulting compound is coupled with butylamine (IX) by means of DCC in acetonitrile.
| 【1】 Endo, Y.; et al.; New estrogenic antagonists bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore. Chem Pharm Bull 2000, 48, 2, 312. |
| 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) | 44847 | 1-ethynyl-4-methoxybenzene; 4-ethynylphenyl methyl ether | C9H8O | 详情 | 详情 | |
| (II) | 44848 | decaborane | H14B10 | 详情 | 详情 | |
| (III) | 44849 | methyl 4-[2-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl]phenyl ether; 1-[6-[2-(4-methoxyphenyl)-2-boriranyl]hexaboranyl]triborirane | C9H18B10O | 详情 | 详情 | |
| (IV) | 44850 | 11-(1lambda(3)-dibromanyl)undecyl tetrahydro-2H-pyran-2-yl ether; 2-[[11-(1lambda(3)-dibromanyl)undecyl]oxy]tetrahydro-2H-pyran | C16H32Br2O2 | 详情 | 详情 | |
| (V) | 44851 | 12-[3-(4-methoxyphenyl)-3-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl]dodecyl tetrahydro-2H-pyran-2-yl ether; 1-[2-(4-methoxyphenyl)-3-[12-(tetrahydro-2H-pyran-2-yloxy)dodecyl]-2-boriranyl]-6-(1-triboriranyl)hexaborane | C26H50B10O3 | 详情 | 详情 | |
| (VI) | 44852 | 11-[3-(4-methoxyphenyl)-3-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl]-1-undecanol | C20H40B10O2 | 详情 | 详情 | |
| (VII) | 44853 | 3-(4-methoxyphenyl)-3-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl 11-[3-(4-methoxyphenyl)-3-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl]undecanoate | C29H54B20O4 | 详情 | 详情 | |
| (VIII) | 44854 | 11-[3-(4-methoxyphenyl)-3-[6-(1-triboriranyl)hexaboranyl]-2-boriranyl]undecanoic acid | C20H38B10O3 | 详情 | 详情 | |
| (IX) | 39041 | butylamine; 1-butanamine | 109-73-9 | C4H11N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Diazotization of 5-aminobenzo[b]thiophene 1,1-dioxide (I), followed by treatment with sulfur dioxide and cupric chloride gives rise to the sulfonyl chloride (II). Subsequent condensation of acid chloride (II) with butylamine (III) produces the corresponding sulfonamide.
| 【1】 Villar, R.; et al.; New hydrophobic benzo[b]thiophenesulfonamide 1,1-dioxide as potential antineoplastic agents. Drugs Fut 2002, 27, Suppl. A. |
合成路线4
该中间体在本合成路线中的序号：(III)The Ugi reaction between 1-benzodioxanylmethyl-4-piperidone (I), N-Boc-leucine (II), butylamine (III), and isonitrile-bound resin produces the diamide resin (IV). Removal of the N-Boc group of (IV), followed by cyclative cleavage of the deprotected amino amide resin (V), affords the target spiro diketopiperazine derivative.
| 【1】 Habashita, H.; et al.; Discovery of potent CCR5-antagonistic anti-HIV agents using newly generated GPCR-targeted combinatorial library. 22nd Symp Med Chem (Nov 27 2002, Shizuoka) 2002, Abst 1P-05. |
| 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) | 61279 | 1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-piperidinone | C14H17NO3 | 详情 | 详情 | |
| (II) | 31818 | N-(tert-butoxycarbonyl)leucine | C11H21NO4 | 详情 | 详情 | |
| (III) | 39041 | butylamine; 1-butanamine | 109-73-9 | C4H11N | 详情 | 详情 |
| (IV) | 61280 | tert-butyl 1-{[[4-(aminocarbonyl)-1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-piperidinyl](butyl)amino]carbonyl}-3-methylbutylcarbamate | C30H48N4O6 | 详情 | 详情 | |
| (V) | 61281 | 4-[(2-amino-4-methylpentanoyl)(butyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-piperidinecarboxamide | C25H40N4O4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IV)The cyclization of (3R)-N-Boc-3-cyclohexyl-D-serine (I) with 1-benzylpiperidin-4-one (II), benzyl isonitrile (III) and butylamine (IV) in refluxing methanol gives the piperidine derivative (V), whose Boc group is removed by treatment with TFA in dichloromethane, yielding compound (VI). The cyclization of (VI) by means of AcOH in hot toluene affords the spiro[piperazine-2,4'-piperidine] derivative (VII), which is hydrogenated in methanol over palladium hydroxide on carbon to cleave the benzyl protecting group and provide the unprotected spiro derivative (VIII). Finally, this compound is reductocondensed with 4-(4-formylphenoxy)benzoic acid (IX) by means of sodium triacetoxyborohydride in DMF/AcOH to give the target spiro[piperazine-2,4'-piperidine] derivative.
| 【1】 Shibayama, S.; Hamano, S.; Takaoka, Y.; Habashita, H. (Ono Pharmaceutical Co., Ltd.); Triazaspiro[5.5]undecane derivs. and drugs containing the same as the active ingredient. EP 1378510; WO 0274770 . |
| 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) | 64663 | (2R,3R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexyl-3-hydroxypropanoic acid | C14H25NO5 | 详情 | 详情 | |
| (II) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (III) | 16730 | 1-(Isocyanatomethyl)benzene; Benzyl Isocyanate | 3173-56-6 | C8H7NO | 详情 | 详情 |
| (IV) | 39041 | butylamine; 1-butanamine | 109-73-9 | C4H11N | 详情 | 详情 |
| (V) | 64664 | tert-butyl (1R)-2-[{1-benzyl-4-[(benzylamino)carbonyl]-4-piperidinyl}(butyl)amino]-1-[(R)-cyclohexyl(hydroxy)methyl]-2-oxoethylcarbamate | C38H56N4O5 | 详情 | 详情 | |
| (VI) | 64665 | 4-[[(2R,3R)-2-amino-3-cyclohexyl-3-hydroxypropanoyl](butyl)amino]-N,1-dibenzyl-4-piperidinecarboxamide | C33H48N4O3 | 详情 | 详情 | |
| (VII) | 64666 | (3R)-9-benzyl-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione | C26H39N3O3 | 详情 | 详情 | |
| (VIII) | 64667 | (3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-1,4,9-triazaspiro[5.5]undecane-2,5-dione | C19H33N3O3 | 详情 | 详情 | |
| (IX) | 64668 | 4-(4-formylphenoxy)benzoic acid | C14H10O4 | 详情 | 详情 |