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【结 构 式】 
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【药物名称】Mosapride citrate, TAK-370, AS-4370, Gasmotin 【化学名称】(±)-4-Amino-5-chloro-2-ethoxy-N-[4-(4-fluorobenzyl)morpholin-2-ylmethyl]benzamide citrate dihydrate 【CA登记号】144256-27-9 (anhydrous free base), 112885-41-3 (anhydrous free base non-specified stereoch.), 112885-42-4 (anhydrous non-specifi 【 分 子 式 】C27H37ClFN3O12 【 分 子 量 】650.06024 |
【开发单位】Dainippon Pharmaceutical (Originator), CyberPharm (Marketer), AstraZeneca (Licensee), Takeda (Licensee) 【药理作用】Esophageal Diseases, Treatment of, Gastric Emptying Disorders,Treatment of of, Gastroesophageal Reflux Disease, Agents for, GASTROINTESTINAL DRUGS, Non-Ulcer Dyspepsia, Agents for, Prokinetic Agents, 5-HT4 Agonists |
合成路线1
The starting compounds (IV) and (VII) are obtained as follows: a) Methyl 4-acetylamino-2-hydroxybenzoate (I) is converted to the 2-ethoxy derivative (II) with ethyl iodide, and then chlorination of (II) with N-chlorosuccinimide followed by alkaline hydrolysis of (III) gives benzoic acid (IV). b) The reaction of 2-[(4-fluorobenzyl)amino]ethanol (V) with N-(2,3-epoxypropyl)phthalimide (VI), followed by treatment with concentrated sulfuric acid, affords intermediate (VII). The condensation of 4-Amino-5-chloro-2-ethoxybenzoic acid (IV) with 4-(4-fluorobenzyl)-2-(methylamino) morpholine (VII) by means of ethyl chloroformate and triethylamine in CHCl3 gives 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl] benzamide, which is converted to mosapride citrate, by treatment with citric acid.
| 【1】 Kato, S.; Yoshida, N.; Ito, T.; Mosapride Citrate. Drugs Fut 1993, 18, 6, 513. |
| 【2】 Kato, S.; Morie, T.; Hino, K.; Kon, T.; Naruto, S.; Yoshida, N.; Karasawa, T.; Matsumoto, J.; Novel benzamides as selective and potent gastrokinetic agents. 1. Synthesis and structure-activity relationships of N[4-(2-morpholinyl)alkyl]benzamides. J Med Chem 1990, 33, 5, 1406-13. |
| 【3】 Kato, S.; Morie, T.; Hino, K.; Kon, T.; Naruto, S.; Yoshida, N.; Karasawa, T.; Matsumoto, J.; Novel benzamides as selective and potent gastrokinetic agents. 1. Synthesis and structure-activity relationships of N[4-(2-morpholinyl)alkyl]benzamides. J Med Chem 1990, 33, 5, 1406-13. |
| 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) | 12330 | methyl 4-(acetamido)-2-hydroxybenzoate | C10H11NO4 | 详情 | 详情 | |
| (II) | 12331 | Methyl 4-acetamido-2-ethoxybenzoate; methyl 4-(acetamido)-2-ethoxybenzoate | 59-06-3 | C12H15NO4 | 详情 | 详情 |
| (III) | 12332 | methyl 4-(acetamido)-5-chloro-2-ethoxybenzoate | C12H14ClNO4 | 详情 | 详情 | |
| (IV) | 12333 | 4-Amino-5-chloro-2-ethoxybenzoic acid | C9H10ClNO3 | 详情 | 详情 | |
| (V) | 12334 | 2-[(4-Fluorobenzyl)amino]-1-ethanol | C9H12FNO | 详情 | 详情 | |
| (VI) | 12335 | 2-(2-Oxiranylmethyl)-1H-isoindole-1,3(2H)-dione; N-(2,3-Epoxypropyl)phtalimide | 5455-98-1 | C11H9NO3 | 详情 | 详情 |
| (VII) | 12336 | [4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methylamine; [4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methanamine; 2-Aminomethyl-4-(4-fluorobenzyl)morpholine | 112914-13-3 | C12H17FN2O | 详情 | 详情 |
合成路线2
The synthesis of the optical enantiomers of mosapride has been described: The reductocondensation of 4-fluorobenzaldehyde (I) with ethanolamine (II) by means of NaBH4 and NaHCO3 in refluxing methanol gives 2-(4-fluorobenzylamino)ethanol (III), which is condensed with epichlorohydrin (IV) to yield the diol (V). Compound (V), without isolation, is cyclized with conc. H2SO4 to afford 2-(chloromethyl)-4-(4-fluorobenzyl)morpholine (VI), which is treated with refluxing water-formamide to afford the corresponding methanol derivative (VII). Tosylation of (VII) with tosyl chloride and triethylamine/4-(dimethylamino)pyridine in dichloromethane gives the tosylate (VIII) as a racemic mixture. The optical resolution of (VIII) with N-(p-toluenesulfonyl)-L-glutamic acid in methanol affords the (S)-tosylate [(S)-IX] and the (R)-tosylate [(R)-IX]. The reaction of both [(S)-IX] and [(R)-IX] with sodium azide followed by reduction with bis(2-methoxyethoxy)aluminum hydride (vitride) gives the chiral amines [(S)-X] and [(R)-X], which are finally condensed with 4-amino-5-chloro-2-ethoxybenzoic acid (XI) by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (WSC) in dichloromethane, yielding the (S)- and (R)-enantiomers of mosapride.
| 【1】 Morie, T.; Kato, S.; Harada, H.; Yoshida, N.; Matsumoto, J.; Synthesis and biological activities of the optical isomers of (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide (mosapride). Chem Pharm Bull 1994, 42, 4, 877. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| ((S)-IX) | 12345 | [(2S)-4-(4-fluorobenzyl)-1,4-oxazinan-2-yl]methyl phenylmethanesulfonate | C19H22FNO4S | 详情 | 详情 | |
| ((R)-IX) | 12346 | [(2R)-4-(4-fluorobenzyl)-1,4-oxazinan-2-yl]methyl phenylmethanesulfonate | C19H22FNO4S | 详情 | 详情 | |
| ((R)-X) | 12347 | [(2R)-4-(4-Fluorobenzyl)morpholinyl]methanamine; [(2R)-4-(4-Fluorobenzyl)morpholinyl]methylamine | C12H17FN2O | 详情 | 详情 | |
| ((S)-X) | 12348 | [(2S)-4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methylamine; [(2S)-4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methanamine | C12H17FN2O | 详情 | 详情 | |
| (I) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (II) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (III) | 12334 | 2-[(4-Fluorobenzyl)amino]-1-ethanol | C9H12FNO | 详情 | 详情 | |
| (IV) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (V) | 12341 | 1-Chloro-3-[(4-fluorobenzyl)(2-hydroxyethyl)amino]-2-propanol | C12H17ClFNO2 | 详情 | 详情 | |
| (VI) | 12342 | 2-(Chloromethyl)-4-(4-fluorobenzyl)morpholine | C12H15ClFNO | 详情 | 详情 | |
| (VII) | 12343 | [4-(4-Fluorobenzyl)-2-morpholinyl]methanol | C12H16FNO2 | 详情 | 详情 | |
| (VIII) | 12344 | [4-(4-fluorobenzyl)-2-morpholinyl]methyl 4-methylbenzenesulfonate | C19H22FNO4S | 详情 | 详情 | |
| (XI) | 12333 | 4-Amino-5-chloro-2-ethoxybenzoic acid | C9H10ClNO3 | 详情 | 详情 |
合成路线3
The chiral sulfonate [(R)-IX] has been obtained in a different way: The cyclization of 2(S)-(benzyloxymethyl)oxirane (XII) with 2-aminoethyl hydrogen sulfate sodium salt (XIII) by means of NaOH in methanol gives 2(R)-(benzyloxymethyl)morpholine (XIV), which is debenzylated by hydrogenation with H2 over Pd/C in ethanol to the chiral alcohol (XV). The condensation of (XV) with 4-fluorobenzyl chloride (XVI) by means of K2CO3 and NaI in refluxing butanone affords 4-(4-fluorobenzyl)-2(R)-(hydroxymethyl)morpholine (XVII), which is finally tosylated with tosyl chloride as before to afford [(R)-IX], already obtained.
| 【1】 Morie, T.; Kato, S.; Harada, H.; Yoshida, N.; Matsumoto, J.; Synthesis and biological activities of the optical isomers of (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide (mosapride). Chem Pharm Bull 1994, 42, 4, 877. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 12346 | [(2R)-4-(4-fluorobenzyl)-1,4-oxazinan-2-yl]methyl phenylmethanesulfonate | C19H22FNO4S | 详情 | 详情 | |
| (XII) | 12350 | Benzyl (2R)oxiranylmethyl ether; (2R)-2-[(Benzyloxy)methyl]oxirane | 14618-80-5 | C10H12O2 | 详情 | 详情 |
| (XIII) | 12351 | Sodium 1-amino-2-(sulfonatooxy)ethane | C2H6NNaO4S | 详情 | 详情 | |
| (XIV) | 12352 | Benzyl (2R)-1,4-oxazinan-2-ylmethyl ether; (2R)-2-[(Benzyloxy)methyl]-1,4-oxazinane | C12H17NO2 | 详情 | 详情 | |
| (XV) | 12353 | (2R)-1,4-Oxazinan-2-ylmethanol | C5H11NO2 | 详情 | 详情 | |
| (XVI) | 12354 | 4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene | 352-11-4 | C7H6ClF | 详情 | 详情 |
| (XVII) | 12344 | [4-(4-fluorobenzyl)-2-morpholinyl]methyl 4-methylbenzenesulfonate | C19H22FNO4S | 详情 | 详情 |
合成路线4
The synthesis of the metabolites of mosapride, 4-amino-5-chloro-2-ethoxy-N-(2-morpholinylmethyl)benzamide (M-1) and 4-amino-5-chloro-2-ethoxy-N-(5-oxo-2-morpholinylmethyl)benzamide (M-2), has been described: 1) The hydrogenolysis of mosapride (I) with H2 over 10% Pd/C in aqueous ethanol/acetic acid gives 4-amino-2-ethoxy-N-(2-morpholinylmethyl)benzamide (II), which is acetylated with acetic anhydride in methanol/CHCl3, yielding the corresponding diacetyl derivative (III). The chlorination of (III) with N-chlorosuccinimide (NCS) in DMF affords the 5-chloro derivative (IV), which is finally deacetylated with refluxing 10% HCl, yielding the metabolite M-1 as the hydrochloride salt.
| 【1】 Kato, S.; Yoshida, N.; Morie, T.; Synthesis and biological activities of metabolites of mosapride, a new gastroprokinetic agent. Chem Pharm Bull 1995, 43, 4, 699. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (M-1) | 63425 | 2-methyl-1,2-dihydropyridine | C14H20ClN3O3 | 详情 | 详情 | |
| (I) | 12356 | 4-Amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-1,4-oxazinan-2-yl]methyl]benzamide | C21H25ClFN3O3 | 详情 | 详情 | |
| (II) | 12357 | 4-Amino-2-ethoxy-N-(1,4-oxazinan-2-ylmethyl)benzamide | C14H21N3O3 | 详情 | 详情 | |
| (III) | 12358 | 4-(Acetamido)-N-[(4-acetyl-1,4-oxazinan-2-yl)methyl]-2-ethoxybenzamide | C18H25N3O5 | 详情 | 详情 | |
| (IV) | 12359 | 4-(Acetamido)-N-[(4-acetyl-1,4-oxazinan-2-yl)methyl]-5-chloro-2-ethoxybenzamide | C18H24ClN3O5 | 详情 | 详情 |
合成路线5
2) The reaction of N-(2,3-epoxypropyl)phthalimide (I) with dibenzylamine (II) at 80 C gives 1-(dibenzylamino)-3-(phthalimido)-2-propanol (III), which is hydrolyzed with refluxing concentrated HCl to afford 1-amino-3-(dibenzylamino)-2-propanol (IV). The acylation of (IV) with chloroacetyl chloride (V) in CHCl3 yields the corresponding chloroacetamide (VI), which is cyclized by means of potassium tert-butoxide in refluxing ethanol to give 6-(dibenzylaminomethyl)morpholin-3-one (VII). The debenzylation of (VII) with H2 over Pd(OH)2/C in ethanol yields 6-(aminomethyl)morpholin-3-one (VIII), which is condensed with 4-(acetamido)-5-chloro-2-ethoxybenzoyl chloride (IX) by means of triethylamine in CHCl3 to afford the monoacetylated derivative of metabolite M-2 (X). Finally, this compound is hydrolyzed with HCl in refluxing ethanol/water to give metabolite M-2. The two final steps of this sequence can also be performed in a single step by condensation of morpholinone (VIII) with 4-amino-5-chloro-2-ethoxybenzoic acid (XI) by means of carbonyldiimidazole (CDI) in THF to afford directly the metabolite M-2 after neutralization with aqueous NH4OH.
| 【1】 Kato, S.; Yoshida, N.; Morie, T.; Synthesis and biological activities of metabolites of mosapride, a new gastroprokinetic agent. Chem Pharm Bull 1995, 43, 4, 699. |
| 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) | 12335 | 2-(2-Oxiranylmethyl)-1H-isoindole-1,3(2H)-dione; N-(2,3-Epoxypropyl)phtalimide | 5455-98-1 | C11H9NO3 | 详情 | 详情 |
| (II) | 12361 | N,N-Dibenzylamine; Dibenzylamine; N-Benzyl(phenyl)methanamine | 103-49-1 | C14H15N | 详情 | 详情 |
| (III) | 12362 | 2-[3-(Dibenzylamino)-2-hydroxypropyl]-1H-isoindole-1,3(2H)-dione | C25H24N2O3 | 详情 | 详情 | |
| (IV) | 12363 | 1-Amino-3-(dibenzylamino)-2-propanol | C17H22N2O | 详情 | 详情 | |
| (V) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VI) | 12365 | 2-Chloro-N-[3-(dibenzylamino)-2-hydroxypropyl]acetamide | C19H23ClN2O2 | 详情 | 详情 | |
| (VII) | 12366 | 6-[(Dibenzylamino)methyl]-3-morpholinone | C19H22N2O2 | 详情 | 详情 | |
| (VIII) | 12367 | 6-(Aminomethyl)-3-morpholinone | C5H10N2O2 | 详情 | 详情 | |
| (IX) | 12368 | 4-(Acetamido)-5-chloro-2-ethoxybenzoyl chloride | C11H11Cl2NO3 | 详情 | 详情 | |
| (X) | 12369 | 4-(Acetamido)-5-chloro-2-ethoxy-N-[(5-oxo-1,4-oxazinan-2-yl)methyl]benzamide | C16H20ClN3O5 | 详情 | 详情 | |
| (XI) | 12333 | 4-Amino-5-chloro-2-ethoxybenzoic acid | C9H10ClNO3 | 详情 | 详情 |
合成路线6
The synthesis of deuterated mosapride citrate has been reported: The cyclization of N-(4-fluorobenzyl)ethanolamine (I) with 2-chloroacrylonitrile (II) in ethyl ether gives 4-(4-fluorobenzyl)morpholine-2-carbonitrile (III), which is submitted to alcoholysis with ethanol and H2SO4, yielding the corresponding ethyl ester (IV). The reduction of (IV) with deuterated sodium borohydride (NaBD4) in THF affords the deuterated hydroxymethyl derivative (V), which is condensed with phthalimide (VI) by means of triphenylphosphine and dimethyl azodicarboxylate (AZDC) in THF to give the N-substituted phthalimide (VII). The cleavage of (VII) with hydrazine hydrate in refluxing ethanol yields the deuterated methylamine derivative (VIII), which is finally condensed with 4-amino-5-chloro-2-ethoxybenzoic acid (IX) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDCD) in dichloromethane, and treated with citric acid in the usual way.
| 【1】 Kato, S.; Hirokawa, Y.; Synthesis of deuterated mosapride citrate. J Label Compd Radiopharm 1995, 36, 10, 927. |
| 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) | 12334 | 2-[(4-Fluorobenzyl)amino]-1-ethanol | C9H12FNO | 详情 | 详情 | |
| (II) | 12372 | 2-Chloroacrylonitrile | 920-37-6 | C3H2ClN | 详情 | 详情 |
| (III) | 12373 | 4-(4-Fluorobenzyl)-2-morpholinecarbonitrile | C12H13FN2O | 详情 | 详情 | |
| (IV) | 12374 | ethyl 4-(4-fluorobenzyl)-2-morpholinecarboxylate | C14H18FNO3 | 详情 | 详情 | |
| (V) | 12375 | [4-(4-Fluorobenzyl)-2-morpholinyl]methanol | C12H16FNO2 | 详情 | 详情 | |
| (VI) | 12376 | Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione | 85-41-6 | C8H5NO2 | 详情 | 详情 |
| (VII) | 12377 | 2-[[4-(4-Fluorobenzyl)-2-morpholinyl]methyl]-1H-isoindole-1,3(2H)-dione | C20H19FN2O3 | 详情 | 详情 | |
| (VIII) | 12378 | [4-(4-Fluorobenzyl)-2-morpholinyl]methylamine; [4-(4-Fluorobenzyl)-2-morpholinyl]methanamine | C12H17FN2O | 详情 | 详情 | |
| (IX) | 12333 | 4-Amino-5-chloro-2-ethoxybenzoic acid | C9H10ClNO3 | 详情 | 详情 |
合成路线7
Two minor metabolites of mosapride 4-amino-5-chloro-2-ethoxy-3-hydroxy-N-(5-oxo-2-morpholinylmethyl)benzamide (A) and 4-amino-5-chloro-2-ethoxy-3-hydroxy-N-(2-morpholinylmethyl)benzamide (B) have been synthesized as follows: 1) The alkylation of 2,3-dihydroxybenzaldehyde (I) with NaH and ethyl iodide in DMSO gives 2-ethoxy-3-hydroxybenzaldehyde (II), which is nitrated with HNO3 in acetic acid yielding 2-ethoxy-3-hydroxy-4-nitrobenzaldehyde (III). The oxidation of (III) with AgNO3 in methanol/water affords the expected benzoic acid (IV), which is condensed with 2-(aminomethyl)morpholin-5-one (V) by means of carbonyldiimidazole (CDI) in THF giving the corresponding benzamide (VI). The hydrogenation of the nitro group of (VI) with H2 over Pd/C in aqueous ethanol yields 4-amino-2-ethoxy-3-hydroxy-N-(5-oxo-2-morpholinylmethyl)benzamide (VII), which is finally chlorinated to the metabolite (A) with N-chlorosuccinimide in hot DMF. 2) The reaction of the benzoic acid (IV) with SOCl2 in refluxing dichloromethane gives the corresponding acyl chloride (VIII), which is condensed with 2-(aminomethyl)-4-(4-fluorobenzyl)morpholine (IX) by means of triethylamine in dichloromethane to yield the expected amide (X). The debenzylation of (X) with 1-chloroethyl chloroformate (ACE-Cl) and reprotection with di-tert-butyl carbonate affords N-[4-(tert-butoxycarbonyl)morpholin-2-ylmethyl]-2-ethoxy-3-hydroxy-4-nitrobenzamide (XI), which is submitted to a reductive acetylation (H2 over Pd/C in acetic anhydride) giving 4-acetamido-N-[4-(tert-butoxycarbonyl)morpholin-2-ylmethyl]-2-ethoxy-3-hydroxybenzamide (XII). The chlorination of (XII) with N-chlorosuccinimide (NCS) in chloroform/DMS yields the corresponding 5-chlorobenzamide (XIII), which is finally deprotected with refluxing aqueous HCl to afford metabolite (B).
| 【1】 Kato, S.; Morie, T.; Yoshida, N.; Synthesis and biological activity of 4-amino-5-chloro-2-ethoxy-3-hydroxybenzamides, metabolites of a new gastroprokinetic agent, mosapride. Chem Pharm Bull 1996, 44, 8, 1484. |
| 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) | 12393 | 4-Amino-5-chloro-2-ethoxy-3-hydroxy-N-[(5-oxo-1,4-oxazinan-2-yl)methyl]benzamide | C14H18ClN3O5 | 详情 | 详情 | |
| (B) | 12394 | 4-Amino-5-chloro-2-ethoxy-3-hydroxy-N-(1,4-oxazinan-2-ylmethyl)benzamide | C14H20ClN3O4 | 详情 | 详情 | |
| (I) | 12380 | 2,3-Dihydroxybenzaldehyde | 24677-78-9 | C7H6O3 | 详情 | 详情 |
| (II) | 12381 | 2-Ethoxy-3-hydroxybenzaldehyde | C9H10O3 | 详情 | 详情 | |
| (III) | 12382 | 2-Ethoxy-3-hydroxy-4-nitrobenzaldehyde | C9H9NO5 | 详情 | 详情 | |
| (IV) | 12383 | 2-Ethoxy-3-hydroxy-4-nitrobenzoic acid | C9H9NO6 | 详情 | 详情 | |
| (V) | 12367 | 6-(Aminomethyl)-3-morpholinone | C5H10N2O2 | 详情 | 详情 | |
| (VI) | 12385 | 2-Ethoxy-3-hydroxy-4-nitro-N-[(5-oxo-1,4-oxazinan-2-yl)methyl]benzamide | C14H17N3O7 | 详情 | 详情 | |
| (VII) | 12386 | 4-Amino-2-ethoxy-3-hydroxy-N-[(5-oxo-1,4-oxazinan-2-yl)methyl]benzamide | C14H19N3O5 | 详情 | 详情 | |
| (VIII) | 12387 | 2-Ethoxy-3-hydroxy-4-nitrobenzoyl chloride | C9H8ClNO5 | 详情 | 详情 | |
| (IX) | 12336 | [4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methylamine; [4-(4-Fluorobenzyl)-1,4-oxazinan-2-yl]methanamine; 2-Aminomethyl-4-(4-fluorobenzyl)morpholine | 112914-13-3 | C12H17FN2O | 详情 | 详情 |
| (X) | 12389 | 2-Ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]-3-hydroxy-4-nitrobenzamide | C21H24FN3O6 | 详情 | 详情 | |
| (XI) | 12390 | tert-butyl 2-[[(2-ethoxy-3-hydroxy-4-nitrobenzoyl)amino]methyl]-4-morpholinecarboxylate | C19H27N3O8 | 详情 | 详情 | |
| (XII) | 12391 | tert-butyl 2-([[4-(acetamido)-2-ethoxy-3-hydroxybenzoyl]amino]methyl)-4-morpholinecarboxylate | C21H31N3O7 | 详情 | 详情 | |
| (XIII) | 12392 | tert-butyl 2-([[4-(acetamido)-5-chloro-2-ethoxy-3-hydroxybenzoyl]amino]methyl)-4-morpholinecarboxylate | C21H30ClN3O7 | 详情 | 详情 |