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【结 构 式】 
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【分子编号】10456 【品名】Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate 【CA登记号】13831-31-7 |
【 分 子 式 】C4H5ClO3 【 分 子 量 】136.5346 【元素组成】C 35.19% H 3.69% Cl 25.97% O 35.15% |
合成路线1
该中间体在本合成路线中的序号：(II)A new partial synthesis for taxol has been reported: The cyclization of N-(4-methoxyphenyl)benzylideneimine (I) with acetoxyacetyl chloride (II) by means of triethylamine in dichloromethane gives cis-3-acetoxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one (III), which is treated with ceric ammonium nitrate in acetonitrile to afford cis-3-acetoxy-4-phenylazetidin-2-one (IV). Hydrolysis of (IV) with KOH in THF-water yields cis-3-hydroxy-4-phenylazetidin-2-one (V), which is submitted to optical resolution giving the (3R,4S)-isomer (VI). The reaction of (VI) with ethyl vinyl ether (VII) by means of methanesulfonic acid in THF affords (3R,4S)-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one (VIII), which is benzoylated with benzoyl chloride (IX) and butyllithium in hexane to give (X). Opening of the azetidine ring of (X) with KOH in THF-water gives (2R,3S)-3-(benzamido)-2-(1-ethoxyethoxy)propanoic acid (XI), which is cyclized with potassium tert-butoxide and methanesulfonyl chloride to (4S,5R)-5-(1-ethoxyethoxy)-2,4-diphenyl-5,6-dihydro-4H-1,3-oxazin-6-one (XII). Finally, this compound is condensed with 7-O-(triethylsilyl)baccatin III (XIV) [prepared from 10-deacetylbaccatin III (XIII) by successive reaction with triethylsilyl chloride and acetyl chloride] by means of dimethylaminopyridine (DMAP) in pyridine.
| 【1】 Holton, R.A. (University of Florida); Method for preparation of taxol using an oxazinone. US 5015744 . |
| 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) | 10455 | N-(4-Methoxyphenyl)-N-[(Z)-benzylidene]amine; 4-Methoxy-N-[(Z)-benzylidene]aniline | 783-08-4 | C14H13NO | 详情 | 详情 |
| (II) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (III) | 10457 | (3R,4S)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetanyl acetate | C18H17NO4 | 详情 | 详情 | |
| (IV) | 10458 | (3R,4S)-2-oxo-4-phenylazetanyl acetate | C11H11NO3 | 详情 | 详情 | |
| (V) | 63030 | cis-3-Hydroxy-4-phenyl-2-azetanone; (3R*,4S*)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (VI) | 10459 | (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (VII) | 18762 | 1-Ethoxyethylene; Ethyl vinyl ether；Ethoxyethene | 109-92-2 | C4H8O | 详情 | 详情 |
| (VIII) | 10462 | (3R,4S)-3-(1-Ethoxyethoxy)-4-phenyl-2-azetanone | C13H17NO3 | 详情 | 详情 | |
| (IX) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (X) | 10464 | (3R,4S)-1-Benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetanone | C20H21NO4 | 详情 | 详情 | |
| (XI) | 10465 | (2R,3S)-3-(Benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropionic acid | C20H23NO5 | 详情 | 详情 | |
| (XII) | 10466 | (4S,5R)-5-(1-Ethoxyethoxy)-2,4-diphenyl-4,5-dihydro-6H-1,3-oxazin-6-one | C20H21NO4 | 详情 | 详情 | |
| (XIII) | 10467 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | 32981-86-5 | C29H36O10 | 详情 | 详情 |
| (XIV) | 10468 | (1S,2S,3R,4S,7R,9R,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C37H52O11Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The synthesis of tritium-labeled taxol [3''-3H]-taxol has been described: The reaction of baccatin III (I) with chlorotriethylsilane in pyridine gives the protected compound (II), which is condensed with cis-1-benzoyl-4-(3-bromophenyl)-3-(triethylsilyloxy)azetidin-2-one (III) by means of butyllithium in THF, yielding 3''-bromo-2',7-bis-O-(triethylsilyl)taxol (IV). The deprotection of (IV) with pyridine and 48% HF in THF affords 3''-bromotaxol (V), which is finally debrominated with tritium by means of Pd/C and triethylamine in THF. The starting azetidinone (III) is obtained as follows: The condensation of 3-bromobenzaldehyde (VI) with 4-methoxyaniline (VII) in refluxing benzene gives the enamine (VIII), which is cyclized with acetoxyacetyl chloride (IX) by means of triethylamine in dichloromethane, yielding cis-3-acetoxy-4-(3-bromophenyl)-1-(4-methoxyphenyl)azetidin-2-one (X). The reaction of (X) with ceric ammonium nitrate (CAN) in acetonitrile affords cis-3-acetoxy-4-(3-bromophenyl)azetidin-2-one (XI), which is deacetylated with KOH in THF-water giving cis-4-(3-bromophenyl)-3-hydroxyazetidin-2-one (XII). The silylation of (XII) with chlorotriethylsilane in pyridine yields cis-4-(3-bromophenyl)-3-(triethylsilyloxy)azetidin-2-one (XIII), which is finally benzoylated with benzoyl chloride (XIV) and butyllithium in THF to afford the desired azetidinone (III).
| 【1】 Taylor, G.F.; Thornton, S.S.; Tallent, C.R.; Kepler, J.A.; Synthesis of [3''-3H]taxol and [13-3H]taxol. J Label Compd Radiopharm 1993, 33, 6, 501. |
| 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) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 | |
| (II) | 10473 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C37H52O11Si | 详情 | 详情 | |
| (III) | 10474 | (3R,4S)-1-Benzoyl-4-(3-bromophenyl)-3-[(triethylsilyl)oxy]-2-azetidinone | C22H26BrNO3Si | 详情 | 详情 | |
| (IV) | 10475 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-(3-bromophenyl)-2-[(triethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C59H78BrNO14Si2 | 详情 | 详情 | |
| (V) | 10476 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-3-(3-bromophenyl)-2-hydroxypropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H50BrNO14 | 详情 | 详情 | |
| (VI) | 10477 | 3-Bromobenzaldehyde; m-Bromobenzaldehyde | 3132-99-8 | C7H5BrO | 详情 | 详情 |
| (VII) | 10478 | p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine | 104-94-9 | C7H9NO | 详情 | 详情 |
| (VIII) | 10479 | N-[(Z)-(3-Bromophenyl)methylidene]-N-(4-methoxyphenyl)amine; N-[(Z)-(3-Bromophenyl)methylidene]-4-methoxyaniline | C14H12BrNO | 详情 | 详情 | |
| (IX) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (X) | 10481 | (2S,3R)-2-(3-bromophenyl)-1-(4-methoxyphenyl)-4-oxoazetanyl acetate | C18H16BrNO4 | 详情 | 详情 | |
| (XI) | 10482 | (2S,3R)-2-(3-bromophenyl)-4-oxoazetanyl acetate | C11H10BrNO3 | 详情 | 详情 | |
| (XII) | 10483 | (3R,4S)-4-(3-Bromophenyl)-3-hydroxy-2-azetanone | C9H8BrNO2 | 详情 | 详情 | |
| (XIII) | 10484 | (3R,4S)-4-(3-Bromophenyl)-3-[(triethylsilyl)oxy]-2-azetanone | C15H22BrNO2Si | 详情 | 详情 | |
| (XIV) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)A new synthesis of paclitaxel has been reported: The cyclization of the 4-methoxyphenylimine of benzaldehyde (I) with acetoxyacetyl chloride (II) by means of triethylamine gives cis-3-acetoxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one (III), which is treated with ceric ammonium nitrate to afford cis-3-acetoxy-4-phenylazetidin-2-one (IV). The hydrolysis of (IV) with KOH in THF/water affords the corresponding hydroxy compound (V), which is submitted to optical resolution by crystallization of the 2-methoxy-2-[2-(trifluoromethyl)phenyl]acetic esters. The (3R,4S)-regioisomer (VI) is protected with ethyl vinyl ether, giving the 1-ethoxyethyl derivative (VII), which is benzoylated with benzoyl chloride and butyllithium to afford (3R,4S)-1-benzoyl-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one (VIII). The condensation of (VIII) with baccatin III (IX) by means of dimethylaminopyridine (DMAP) in pyridine yields the protected paclitaxel derivative (X), which is finally deprotected with HCl in ethanol/water.
| 【1】 Holton, R.A. (University of Florida); Method for preparation of taxol. EP 0400971; US 5336785 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 | |
| (I) | 10455 | N-(4-Methoxyphenyl)-N-[(Z)-benzylidene]amine; 4-Methoxy-N-[(Z)-benzylidene]aniline | 783-08-4 | C14H13NO | 详情 | 详情 |
| (II) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (III) | 10457 | (3R,4S)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetanyl acetate | C18H17NO4 | 详情 | 详情 | |
| (IV) | 10458 | (3R,4S)-2-oxo-4-phenylazetanyl acetate | C11H11NO3 | 详情 | 详情 | |
| (V) | 63030 | cis-3-Hydroxy-4-phenyl-2-azetanone; (3R*,4S*)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (VI) | 10459 | (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (VII) | 10462 | (3R,4S)-3-(1-Ethoxyethoxy)-4-phenyl-2-azetanone | C13H17NO3 | 详情 | 详情 | |
| (VIII) | 10464 | (3R,4S)-1-Benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetanone | C20H21NO4 | 详情 | 详情 | |
| (IX) | 10473 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C37H52O11Si | 详情 | 详情 | |
| (X) | 10505 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C57H73NO15Si | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)A new synthesis of [14C]-labeled paclitaxel has been published: The protection of L-threonine methyl ester (I) with tert-butoxydiphenylchlorosilane (BPS-Cl) gives the compound (II), which is condensed with [14C]-labeled benzaldehyde (III), yielding the imine (IV). The cyclization of (IV) with acetoxyacetyl chloride (V) by means of triethylamine affords the azetidinone (VI), which is deprotected with tetrabutylammonium fluoride to the hydroxy ester (VII). The dehydration of (VII) with p-toluenesulfonyl chloride and triethylamine affords the unsaturated ester (VIII), which by ozonolysis is converted to the oxalimide (IX). Elimination of the oxalyl group with hydrazine gives the labeled azetidinone (X), which is deacetylated to the hydroxyazetidinone (XI) and protected with triethylchlorosilane (TES-Cl) to (XII). The benzoylation of (XII) with benzoyl chloride (XIII) and dimethylaminopyridine (DMAP) yields the corresponding benzoylated compound (XIV), which is then condensed with triethylsilyl-baccatin III (XV) by means of butyllithium to afford silylated labeled paclitaxel (XVI). Finally, this compound is deprotected with HCl. The intermediate silylated baccatin III (XV) is obtained from paclitaxel (XVII) by hydrogenolysis with NaBH4 to baccatin III (XVIII) and silylation with triethylsilyl chloride to (XV).
| 【1】 Walker, D.G.; Swigor, J.E.; Standridge, R.T.; Synthesis of paclitaxel-C3'-C-14. J Label Compd Radiopharm 1995, 36, 5, 479. |
| 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) | 10674 | (2S,3R)-3-Hydroxy-1-methoxy-1-oxo-2-butanaminium chloride | C5H12ClNO3 | 详情 | 详情 | |
| (II) | 10675 | methyl (2S,3R)-2-amino-3-methoxybutanoate | C21H29NO4Si | 详情 | 详情 | |
| (III) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 44663 | benzaldehyde | C7H6O | 详情 | 详情 | |
| (IV) | 10677 | methyl (2S,3R)-3-methoxy-2-[[(E)-benzylidene]amino]butanoate | C28H33NO4Si | 详情 | 详情 | |
| (IV) | 44664 | methyl (2S,3R)-3-methoxy-2-[[(E)-benzylidene]amino]butanoate | C13H17NO3 | 详情 | 详情 | |
| (V) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (VI) | 10679 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-methoxybutanoate | C32H37NO7Si | 详情 | 详情 | |
| (VI) | 44665 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-methoxybutanoate | C17H21NO6 | 详情 | 详情 | |
| (VII) | 10680 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-hydroxybutanoate | C16H19NO6 | 详情 | 详情 | |
| (VII) | 44666 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-hydroxybutanoate | C16H19NO6 | 详情 | 详情 | |
| (VIII) | 10681 | methyl (Z)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-butenoate | C16H17NO5 | 详情 | 详情 | |
| (VIII) | 44667 | methyl (Z)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-butenoate | C16H17NO5 | 详情 | 详情 | |
| (IX) | 10682 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (IX) | 44668 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (X) | 10683 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (X) | 44669 | (3R,4S)-2-oxo-4-phenylazetidinyl acetate | C11H11NO3 | 详情 | 详情 | |
| (XI) | 10459 | (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (XI) | 44670 | (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone | C9H9NO2 | 详情 | 详情 | |
| (XII) | 10685 | (3R,4S)-4-Phenyl-3-[(triethylsilyl)oxy]-2-azetidinone | C15H23NO2Si | 详情 | 详情 | |
| (XII) | 44673 | (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone | C9H9NO2 | 详情 | 详情 | |
| (XIII) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (XIV) | 10687 | (3R,4S)-1-Benzoyl-3-hydroxy-4-phenyl-2-azetidinone | C16H13NO3 | 详情 | 详情 | |
| (XIV) | 44671 | (3R,4S)-1-benzoyl-3-hydroxy-4-phenyl-2-azetidinone | C16H13NO3 | 详情 | 详情 | |
| (XV) | 10473 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C37H52O11Si | 详情 | 详情 | |
| (XVI) | 10689 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | n/a | AB | 详情 | 详情 |
| (XVI) | 44672 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H51NO14 | 详情 | 详情 | |
| (XVII) | 10595 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | 33069-62-4 | C47H51NO14 | 详情 | 详情 |
| (XVIII) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VI)Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II). Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst. Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV). Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine. Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII). After saponification of the ester groups of (VII), the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound. Alternatively, amide (VIII) is alkylated by bromoethyl acetate (X), producing (XI). Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid. An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
| 【1】 Lin, Y. (Mallinckrodt Medical Inc.); Cpds. suitable for X-ray visualisation methods. EP 0083964; US 4396598 . |
| 【2】 Dunn, T.J.; White, D.H.; Kneller, M.T.; Jones, M.M.; Doran, N.O. III; Bailey, A.R. (Mallinckrodt Medical Inc.); Process for producing ioversol. WO 9727172 . |
| 【3】 Kneller, M.T.; Bailey, A.R.; Sathe, S.S.; Spears, A.T.; Wisneski, R.C. (Mallinckrodt Medical Inc.); Improved synthesis of ioversol. WO 9323365 . |
| 【4】 Villa, M.; Castaldi, G.; Pozzoli, C.; Russo, L. (Zambon Group SpA); Process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination with thionyl chloride in the presence of a catalyst. WO 9636590 . |
| 【5】 Lin, Y.; Dean, R.T.; Kneller, M.; Wallace, R.A.; McCarthy, W.Z.; White, D.H. (Mallinckrodt Medical Inc.); Process for production of ioversol. WO 9111431 . |
| 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) | 22006 | 5-amino-2,4,6-triiodoisophthalic acid | 35453-19-1 | C8H4I3NO4 | 详情 | 详情 |
| (II) | 31194 | 5-amino-2,4,6-triiodoisophthaloyl dichloride | 37441-29-5 | C8H2Cl2I3NO2 | 详情 | 详情 |
| (III) | 12979 | 3-Amino-1,2-propanediol；3-aminopropane-1,2-diol | 616-30-8 | C3H9NO2 | 详情 | 详情 |
| (IV) | 59316 | 5-amino-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide | C14H18I3N3O6 | 详情 | 详情 | |
| (V) | 59322 | 2-(acetyloxy)-1-({[3-amino-5-({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodobenzoyl]amino}methyl)ethyl acetate | C22H26I3N3O10 | 详情 | 详情 | |
| (VI) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (VII) | 59323 | 2-(acetyloxy)-1-({[3-{[2-(acetyloxy)acetyl]amino}-5-({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodobenzoyl]amino}methyl)ethyl acetate | C26H30I3N3O13 | 详情 | 详情 | |
| (VIII) | 59324 | N~1~,N~3~-bis(2,3-dihydroxypropyl)-5-(glycoloylamino)-2,4,6-triiodoisophthalamide | C16H20I3N3O8 | 详情 | 详情 | |
| (IX) | 33463 | 2-bromoethyl acetate | 927-68-4 | C4H7BrO2 | 详情 | 详情 |
| (X) | 10384 | 2-Chloro-1-ethanol; Ethylene chlorohydrin | 107-07-3 | C2H5ClO | 详情 | 详情 |
| (XI) | 59325 | 2-[[2-(acetyloxy)acetyl]-3,5-bis({[2,3-bis(acetyloxy)propyl]amino}carbonyl)-2,4,6-triiodoanilino]ethyl acetate | C30H36I3N3O15 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)A further synthetic variation for the title compound is based on the acylation of intermediate (I) with acetoxyacetyl chloride (II) to afford (III). Amide alkylation with bromoethyl acetate (IV) furnishes (V). The ester groups of (V) are finally hydrolyzed in aqueous sulfuric acid.
| 【1】 Lin, Y.; Wallace, R.A.; McCarthy, W.Z.; Kneller, M.T.; White, D.H. (Mallinckrodt Medical Inc.); Synthesis of ioversol using a minimal excessof acetoxyacetylchloride. US 5371278 . |
| 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) | 59316 | 5-amino-N~1~,N~3~-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide | C14H18I3N3O6 | 详情 | 详情 | |
| (II) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (III) | 59331 | 2-[(3-{[2-(acetyloxy)acetyl]amino}-5-{[(2,3-bis{[2-(acetyloxy)acetyl]oxy}propyl)amino]carbonyl}-2,4,6-triiodobenzoyl)amino]-1-({[2-(acetyloxy)acetyl]oxy}methyl)ethyl 2-(acetyloxy)acetate | C34H38I3N3O21 | 详情 | 详情 | |
| (IV) | 33463 | 2-bromoethyl acetate | 927-68-4 | C4H7BrO2 | 详情 | 详情 |
| (V) | 59332 | 2-[(3-{[2-(acetyloxy)acetyl][2-(acetyloxy)ethyl]amino}-5-{[(2,3-bis{[2-(acetyloxy)acetyl]oxy}propyl)amino]carbonyl}-2,4,6-triiodobenzoyl)amino]-1-({[2-(acetyloxy)acetyl]oxy}methyl)ethyl 2-(acetyloxy)acetate | C38H44I3N3O23 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(II)TB-2285 was synthesized by acylation of 3,5-diamino-4-chlorobenzonitrile (I) with 2-acetoxyacetyl chloride (II) in pyridine.
| 【1】 Rabasseda, X.; Mealy, N.; Castaner, J.; TYB-2285. Drugs Fut 1995, 20, 7, 686. |
| 【2】 Taguchi, H.; Katsushima, T.; Ban, M.; Watanabe, A. (Toyobo Co., Ltd.); Novel amide cpds. EP 0315112; JP 1989121256 . |
合成路线8
该中间体在本合成路线中的序号：(III)Hydrogenolysis of PNU-100542 (I) removed the benzyloxycarbonyl group and afforded secondary amine (II), which was acylated with (acetoxy)acetyl chloride (III) in the presence of triethylamine to provide amide PNU-142581 (IV). Then, acetate and phthaloyl protecting groups were both removed on treatment with an hydroalcoholic solution of methylamine, and the resulting aminoalcohol PNU-141718 (V) was N-acylated with dichloroacetyl chloride (VI) to yield the desired amide PNU-109230.
| 【1】 Ulanowicz, D.A.; et al.; Synthesis and biological activity of N-acetyl modified analogs of oxazolidinone anticancer agents linezolid and eperezolid. 37th Intersci Conf Antimicrob Agents Chemother (Sept 28-Oct 1, Toronto) 1997, Abst F-21. |
| 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) | 17824 | benzyl 4-(4-[(5S)-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1-piperazinecarboxylate | C30H27FN4O6 | 详情 | 详情 | |
| (II) | 17825 | 2-([(5S)-3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)-1H-isoindole-1,3(2H)-dione | C22H21FN4O4 | 详情 | 详情 | |
| (III) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (IV) | 17827 | 2-[4-(4-[(5S)-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1-piperazinyl]-2-oxoethyl acetate | C26H25FN4O7 | 详情 | 详情 | |
| (V) | 17828 | (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-glycoloyl-1-piperazinyl)phenyl]-1,3-oxazolidin-2-one | C16H21FN4O4 | 详情 | 详情 | |
| (VI) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(XII)The asymmetric 1,3-dipolar cycloaddition of the nitrile oxide resulting from 4-bromo-N-hydroxybenzenecarboximidoyl chloride (I) to allyl alcohol (II) in the presence of (R,R)-diisopropyl tartrate and diethylzinc afforded the (R)-5-(hydroxymethyl)isoxazoline (III). After conversion of (III) to the mesylate (IV), treatment with ammonium hydroxide in a sealed vessel provided primary amine (V), which was then acetylated with Ac2O and pyridine to give amide (VI). Further treatment of (VI) with hexamethylditin and dichlorobis(triphenylphosphine) palladium yielded the trimethylstannyl derivative (VII). Reaction of N-Boc-4-piperidone (VIII) with lithium diisopropylamide and N-phenyl-trifluoromethanesulfonimide at low temperature furnished the corresponding vinyl triflate (IX). Subsequent coupling of (IX) with stannyl derivative (VII) in the presence of tris(dibenzylideneacetone)dipalladium and triphenylarsine gave rise to the N-Boc-tetrahydropyridylphenylisoxazole (X). The Boc group of (X) was then deprotected using trifluoroacetic acid, and the deprotected tetrahydropyridine (XI) was condensed with acetoxyacetyl chloride (XII), yielding the acetoxyacetamide (XIII). The acetate ester of (XIII) was finally hydrolyzed by means of K2CO3 in MeOH.
| 【1】 Ukaji, Y.; et al.; Enantioselective synthesis of 2-isoxazolines via asymmetric 1,3-dipolar cycloaddition of nitrile oxides to achiral allyl alcohols. Chem Lett 1993, 11, 1847. |
| 【2】 Barbachyn, M.R.; Thomas, R.C.; Cleek, G.J. (Pharmacia & Upjohn AB); Isoxazoline derivs. useful as antimicrobials. EP 0920421; US 5990136; WO 9807708 . |
| 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) | 32966 | 4-bromo-N-hydroxybenzenecarboximidoyl chloride | C7H5BrClNO | 详情 | 详情 | |
| (II) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (III) | 32967 | [(5R)-3-(4-bromophenyl)-4,5-dihydro-5-isoxazolyl]methanol | C10H10BrNO2 | 详情 | 详情 | |
| (IV) | 32968 | [(5R)-3-(4-bromophenyl)-4,5-dihydro-5-isoxazolyl]methyl methanesulfonate | C11H12BrNO4S | 详情 | 详情 | |
| (V) | 32969 | [(5R)-3-(4-bromophenyl)-4,5-dihydro-5-isoxazolyl]methylamine; [(5R)-3-(4-bromophenyl)-4,5-dihydro-5-isoxazolyl]methanamine | C10H11BrN2O | 详情 | 详情 | |
| (VI) | 32970 | N-[[(5R)-3-(4-bromophenyl)-4,5-dihydro-5-isoxazolyl]methyl]acetamide | C12H13BrN2O2 | 详情 | 详情 | |
| (VII) | 32971 | N-([(5R)-3-[4-(trimethylstannyl)phenyl]-4,5-dihydro-5-isoxazolyl]methyl)acetamide | C15H22N2O2Sn | 详情 | 详情 | |
| (VIII) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (IX) | 32972 | tert-butyl 4-[[(trifluoromethyl)sulfonyl]oxy]-3,6-dihydro-1(2H)-pyridinecarboxylate | C11H16F3NO5S | 详情 | 详情 | |
| (X) | 32973 | tert-butyl 4-(4-[(5R)-5-[(acetamido)methyl]-4,5-dihydro-3-isoxazolyl]phenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate | C22H29N3O4 | 详情 | 详情 | |
| (XI) | 32974 | N-([(5R)-3-[4-(1,2,3,6-tetrahydro-4-pyridinyl)phenyl]-4,5-dihydro-5-isoxazolyl]methyl)acetamide | C17H21N3O2 | 详情 | 详情 | |
| (XII) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (XIII) | 32975 | 2-[4-(4-[(5R)-5-[(acetamido)methyl]-4,5-dihydro-3-isoxazolyl]phenyl)-3,6-dihydro-1(2H)-pyridinyl]-2-oxoethyl acetate | C21H25N3O5 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(XI)2-Methylindole (I) was nitrated employing NaNO3 in H2SO4 and the resultant 5-nitroindole (II) was further reduced to the corresponding indoline (III) by means of NaBH3CN in the presence of HOAc. Catalytic hydrogenation of the nitro group of (III) over Pd/C furnished diamine (IV), which was converted to the bis-carbamate (V) by treatment with benzyl chloroformate. Oxazolidinone (VII) was then obtained by condensation of carbamate (V) with (R)-glycidyl butyrate (VI) in the presence of BuLi at -78 C. After conversion of alcohol (VII) to the corresponding nosylate (VIII), displacement of its sulfonate group with ammonium hydroxide gave rise to the primary amine (IX). Acetylation of amine (IX), followed by hydrogenolysis of the remaining N-benzyloxycarbonyl group, yielded acetamide (X). The indoline N of (X) was then acylated by acetoxyacetyl chloride (XI) to produce amide (XII). The title compound was then obtained by smooth hydrolysis of the acetoxy group of (XII) with K2CO3, followed by separation of the resultant mixture of diastereoisomers by chiral HPLC.
| 【1】 Genin, M.J.; Barbachyn, M.R.; Grega, K.C.; et al.; The potentiating effect of remote chirality on the antibacterial activity of a series of 2-substituted indolinyl phenyloxazolidinones. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1042. |
| 【2】 Hester, J.B. Jr.; Barbachyn, M.R.; Johnson, P.D.; Genin, M.J. (Pharmacia Corp.); Bicyclic oxazolidinones as antibacterial agent. EP 1181288; US 6387896; WO 0073301 . |
| 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) | 28747 | 2-methyl-1H-indole | 95-20-5 | C9H9N | 详情 | 详情 |
| (II) | 55948 | 2-methyl-5-nitro-1H-indole; 2-Methyl-5-nitroindole | 7570-47-0 | C9H8N2O2 | 详情 | 详情 |
| (III) | 55949 | 2-methyl-5-nitroindoline | C9H10N2O2 | 详情 | 详情 | |
| (IV) | 55950 | 2-methyl-2,3-dihydro-1H-indol-5-ylamine; 2-methyl-5-indolinamine | C9H12N2 | 详情 | 详情 | |
| (V) | 55951 | benzyl 5-{[(benzyloxy)carbonyl]amino}-2-methyl-1-indolinecarboxylate | C25H24N2O4 | 详情 | 详情 | |
| (VI) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (VII) | 55952 | benzyl 5-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-methyl-1-indolinecarboxylate | C21H22N2O5 | 详情 | 详情 | |
| (VIII) | 55953 | benzyl 2-methyl-5-[(5R)-5-({[(3-nitrophenyl)sulfonyl]oxy}methyl)-2-oxo-1,3-oxazolidin-3-yl]-1-indolinecarboxylate | C27H25N3O9S | 详情 | 详情 | |
| (IX) | 55954 | benzyl 5-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-methyl-1-indolinecarboxylate | C21H23N3O4 | 详情 | 详情 | |
| (X) | 55955 | N-{[(5S)-3-(2-methyl-2,3-dihydro-1H-indol-5-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | C15H19N3O3 | 详情 | 详情 | |
| (XI) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (XII) | 55956 | 2-(5-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl acetate | C19H23N3O6 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(II)In a related synthetic strategy, acylation of 2-bromoaniline (I) with acetoxyacetyl chloride (II) affords the acetoxy acetanilide (III). Alkylation of amide (III) with iodomethane and NaH leads to the N-methyl amide (IV). Then, Stille coupling of aryl bromide (IV) with tributyl (1-ethoxyvinyl)tin (V) gives rise to the enol ether (VI). Bromination of (VI) with N-bromosuccinimide in moist THF, followed by displacement of the resultant bromo ketone (VII) with NaN3 provides azido ketone (VIII). The key oxazole (X) is then obtained by condensation of azido ketone (VIII) with isothiocyanate (IX) in the presence of PPh3. Alkaline hydrolysis of the acetate ester (X) yields alcohol (XI), which is converted to mesylate (XII) by means of methanesulfonyl chloride and triethylamine. The mesylate group is finally displaced with morpholine (XIII) to furnish the title compound.
| 【1】 Dhar, T.G.M.; Guo, J.; Shen, Z.; et al.; A modified approach to 2-(N-aryl)-1,3-oxazoles: application to the synthesis of the IMPDH inhibitor BMS-337197 and analogues. Org Lett 2002, 4, 12, 2091. |
| 【2】 Dhar, T.G.M.; et al.; Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]-amino]-5-oxazolyl]phenyl]-N-methyl-4-morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity. J Med Chem 2002, 45, 11, 2127. |
| 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) | 27739 | 2-bromoaniline | 615-36-1 | C6H6BrN | 详情 | 详情 |
| (II) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (III) | 61853 | 2-(2-bromoanilino)-2-oxoethyl acetate | C10H10BrNO3 | 详情 | 详情 | |
| (IV) | 61854 | 2-[2-bromo(methyl)anilino]-2-oxoethyl acetate | C11H12BrNO3 | 详情 | 详情 | |
| (V) | 19760 | ethyl 1-(tributylstannyl)vinyl ether; tributyl(1-ethoxyvinyl)stannane | 97674-02-7 | C16H34OSn | 详情 | 详情 |
| (VI) | 61855 | 2-[2-(1-ethoxyvinyl)(methyl)anilino]-2-oxoethyl acetate | C15H19NO4 | 详情 | 详情 | |
| (VII) | 61856 | 2-[2-(2-bromoacetyl)(methyl)anilino]-2-oxoethyl acetate | C13H14BrNO4 | 详情 | 详情 | |
| (VIII) | 61857 | 2-[2-(2-azidoacetyl)(methyl)anilino]-2-oxoethyl acetate | C13H14N4O4 | 详情 | 详情 | |
| (IX) | 61697 | 3-methoxy-4-(1,3-oxazol-5-yl)phenyl isothiocyanate; 5-(4-isothiocyanato-2-methoxyphenyl)-1,3-oxazole | C11H8N2O2S | 详情 | 详情 | |
| (X) | 61858 | 2-[2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}(methyl)anilino]-2-oxoethyl acetate | C24H22N4O6 | 详情 | 详情 | |
| (XI) | 61859 | 2-hydroxy-N-(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)-N-methylacetamide | C22H20N4O5 | 详情 | 详情 | |
| (XII) | 61860 | 2-[2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}(methyl)anilino]-2-oxoethyl methanesulfonate | C23H22N4O7S | 详情 | 详情 | |
| (XIII) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(II)The title trans beta-lactam is obtained by condensation of imine (I) with acetyloxyacetyl chloride (II) in the presence of Et3N in cold CH2Cl2 under Staudinger reaction conditions. (1,2)
| 【1】 Banik, N.K.; Becker, F.F.; Unprecedented stereoselectivity in the Staudinger reaction with polycyclic aromatic imines. Tetrahedron Lett 2000, 41, 34, 6551. |
| 【2】 Banik, I.; Becker, F.F.; Banik, B.K.; Stereoselective synthesis of beta-lactams with polyaromatic imines: Entry to new and novel anticancer agents. J Med Chem 2003, 46, 1, 12. |
合成路线13
该中间体在本合成路线中的序号：(VII)3,4,5-Trifluorobenzaldehyde (I) is converted into oxime (II) upon treatment with hydroxylamine in aqueous EtOH. Subsequent oxidation of oxime (II) with N-chlorosuccimide produces the hydroximinoyl chloride (III). In situ conversion of (III) to the corresponding nitrile oxide, followed by cycloaddition with N-allyl acetamide (IV) generates the racemic isoxazoline (V). After resolution of (V) by means of chiral HPLC, displacement of the para-fluoride group with piperazine in hot DMSO furnishes (VI). Acylation of piperazine (VI) by means of acetoxyacetyl chloride (VII) gives rise to amide (VIII). Finally, methanolysis of the acetoxy group of (VIII) in the presence of K2CO3 leads to the target hydroxyacetylpiperazine derivative. (1,2)
| 【1】 Identification of phenylisoxazolines as novel and viable antibacterial agents active against Gram-positive pathogens. J Med Chem 2003, 46, 2, 284. |
| 【2】 Thomas, R.C.; Barbachyn, M.R.; Morris, J.; Wishka, D.G.; Cleek, G.J. (Pfizer Inc.); Substd. aminophenyl isoxazoline derivs. useful as antimicrobials. JP 2002503655; US 6069141; WO 9941244 . |
| 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) | 64391 | 3,4,5-trifluorobenzaldehyde | C7H3F3O | 详情 | 详情 | |
| (II) | 64392 | 3,4,5-trifluorobenzaldehyde oxime | C7H4F3NO | 详情 | 详情 | |
| (III) | 64393 | 3,4,5-trifluoro-N-hydroxybenzenecarboximidoyl chloride | C7H3ClF3NO | 详情 | 详情 | |
| (IV) | 64394 | N-(2-propenyl)acetamide | C5H9NO | 详情 | 详情 | |
| (V) | 64395 | N-{[3-(3,4,5-trifluorophenyl)-4,5-dihydro-5-isoxazolyl]methyl}acetamide | C12H11F3N2O2 | 详情 | 详情 | |
| (VI) | 64396 | N-({3-[3,5-difluoro-4-(1-piperazinyl)phenyl]-4,5-dihydro-5-isoxazolyl}methyl)acetamide | C16H20F2N4O2 | 详情 | 详情 | |
| (VII) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (VIII) | 64397 | 2-[4-(4-{5-[(acetylamino)methyl]-4,5-dihydro-3-isoxazolyl}-2,6-difluorophenyl)-1-piperazinyl]-2-oxoethyl acetate | C20H24F2N4O5 | 详情 | 详情 |