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【结 构 式】 
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【药物名称】Indinavir sulfate, MK-639, L-735524, Crixivan 【化学名称】2(R)-Benzyl-5-[2(S)-(N-tert-butylcarbamoyl)-4-(3-pyridylmethyl)piperazin-1-yl]-4(S)-hydroxy-N-[2(R)-hydroxyindan-1(S)-yl]pentanamide sulfate (1:1) 【CA登记号】157810-81-6, 150378-17-9 (free base), 180683-37-8 (hydrate) 【 分 子 式 】C36H49N5O8S 【 分 子 量 】711.88463 |
【开发单位】Merck & Co. (Originator), Banyu (Not Determined) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, HIV Protease Inhibitors |
合成路线1
1) The reaction of cis-(1S,2R)-indanediol (I) with acetonitrile and concentrated H2SO4 gives cis-(1S,2R)-1-aminoindan-2-ol (II), which is cyclocondensed with 3-phenylpropionyl chloride (III), isopropenyl methyl ether and triethylamine to yield the acetonide amide (IV). The condensation of amide (IV) with (S)-(+)-glycidyl p-toluenesulfonate (V) in the presence of lithium hexamethyldisylazide (LHS) affords the chiral epoxide (VI), which is condensed with 4-(tert-butoxycarbonyl)-N-tert-butylpiperazine-2(S)-carboxamide (VII) in refluxing isopropyl acetate and deprotected with aqueous HCl to give the dihydroxy-diamide (VIII). Finally, this compound is condensed with 3-(chloromethyl)pyridine (IX) by means of triethylamine in DMF. 2) The amide (IV) can also be alkylated with allyl bromide and butyllithium to the pentenyl amide (X), which is diastereoselectively converted to the chiral iodohydrine (XI) by means of N-iodosuccinimide (NIS). Finally, this compound is cyclized in basic medium, yielding the epoxide (VI), already obtained.
| 【1】 Maligres, P.E.; Upadhyay, V.; Rossen, K.; Cianciosi, S.J.; Purick, R.M.; Eng, K.K.; Reamer, R.A.; Askin, D.; Volante, R.P.; Reider, P.J.; Diastereoselective syn-epoxidation of 2-alkyl-4-enamides to epoxyamides: Synthesis of the Merck HIV-1 protease inhibitor epoxide intermediate. Tetrahedron Lett 1995, 36, 13, 2195-8. |
| 【2】 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600. |
| 【3】 Askin, D.; Volante, R.P.; Eng, K.K. (Merck & Co., Inc.); Process for making HIV protease inhibitors. WO 9502584 . |
| 【4】 Verhoeven, T.R.; Roberts, E.F.; Senanayake, C.H.; Ryan, K.M. (Merck & Co., Inc.); Regiospecific processes to make cis-1-amino-2-alkanol from diol or halohydrin. US 5449830 . |
| 【5】 Askin, D.; Eng, K.K.; Rossen, K.; Purick, R.M.; Wells, K.M.; Volante, R.P.; Reider, P.J.; Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524. Tetrahedron Lett 1994, 35, 5, 673-6. |
| 【6】 Dorsey, B.D.; Levin, R.B.; McDaniel, S.L.; et al.; L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor. J Med Chem 1994, 37, 21, 3443-51. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 | |
| 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 | |
| (I) | 16238 | (1S,2R)-2,3-dihydro-1H-indene-1,2-diol | 67528-22-7 | C9H10O2 | 详情 | 详情 |
| (II) | 16239 | (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol; Cis-(1S)-1-amino-2,3-dihydro-1H-inden-2-ol | 126456-43-7 | C9H11NO | 详情 | 详情 |
| (III) | 16240 | 3-phenylpropanoyl chloride; Hydrocinnamoylchloride | 645-45-4 | C9H9ClO | 详情 | 详情 |
| (IV) | 16241 | 1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-3-phenyl-1-propanone | C21H23NO2 | 详情 | 详情 | |
| (V) | 16242 | (2R)oxiranylmethyl 4-methylbenzenesulfonate; (2R)-(-)-Glycidyl tosylate | 113826-06-5 | C10H12O4S | 详情 | 详情 |
| (VI) | 16243 | (2R)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-3-[(2S)oxiranyl]-1-propanone | C24H27NO3 | 详情 | 详情 | |
| (VII) | 16244 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | 150323-35-6 | C14H27N3O3 | 详情 | 详情 |
| (VIII) | 16245 | (2S)-1-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-N-(tert-butyl)-2-piperazinecarboxamide | C30H42N4O4 | 详情 | 详情 | |
| (IX) | 15793 | 3-(Chloromethyl)pyridine | 3099-31-8 | C6H6ClN | 详情 | 详情 |
| (X) | 16247 | (2S)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-4-penten-1-one | C24H27NO2 | 详情 | 详情 | |
| (XI) | 16248 | (2R,4S)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-4-hydroxy-5-iodo-1-pentanone | C24H28INO3 | 详情 | 详情 |
合成路线2
3) The alkylation of 5(S)-(tert-butyldimethylsilyloxymethyl)tetrahydrofuran-2-one (XII) by means of benzyl bromide (XIII) and lithium diisopropylamide (LDA) gives the corresponding 3(R)-benzyl derivative (XIV), which is deprotected with aqueous HF, yielding the hydroxymethyl compound (XV). The esterification of (XV) with trifluoromethanesulfonic anhydride affords the corresponding triflate (XVI), which is condensed with the chiral piperazine (VII) by means of diisopropylethylamine in isopropanol, giving the substituted furanone (XVII). Ring opening of the furanone (XVII) with LiOH, DME and imidazole yields the substituted hydroxypentanamide (XVIII), which is protected with tert-butyldimethylsilyl chloride to afford the protected amide (XIX). The trans-amidation of (XIX) with 2-hydroxyindan-1-amine (II) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBt) in DMF gives the protected dihydroxy diamide (XX), which is deprotected with trimethylsilyl triflate, affording the dihydroxy diamide (VII), already obtained. This compound is then alkylated with 3-(chloromethyl)pyridine (IX) as before.
| 【1】 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600. |
| 【2】 Vacca, J.P.; Holloway, M.K.; Dorsey, B.D.; Hungate, R.W.; Guare, J.P. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0541168; JP 1993279337; WO 9309096 . |
| 【3】 Vacca, J.P.; Guare, J.P.; Dorsey, B.D.; Holloway, M.K.; Hungate, R.W. (Merck & Co., Inc.); HIV protease inhibitors in pharmaceutical combinations for the treatment of AIDS. EP 0617968; JP 1996508496; WO 9422480 . |
| 【4】 Vacca, J.P.; Dorsey, B.D.; Guare, J.P.; Holloway, M.K.; Hungate, R.W.; Levin, R.B. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0696277; JP 1996509980; US 5413999; WO 9426717 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 16239 | (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol; Cis-(1S)-1-amino-2,3-dihydro-1H-inden-2-ol | 126456-43-7 | C9H11NO | 详情 | 详情 |
| (VII) | 16244 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | 150323-35-6 | C14H27N3O3 | 详情 | 详情 |
| (VIII) | 16245 | (2S)-1-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-N-(tert-butyl)-2-piperazinecarboxamide | C30H42N4O4 | 详情 | 详情 | |
| (IX) | 15793 | 3-(Chloromethyl)pyridine | 3099-31-8 | C6H6ClN | 详情 | 详情 |
| (XII) | 16249 | (5S)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)dihydro-2(3H)-furanone | C11H22O3Si | 详情 | 详情 | |
| (XIII) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (XIV) | 16251 | (3R,5S)-3-benzyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)dihydro-2(3H)-furanone | C18H28O3Si | 详情 | 详情 | |
| (XV) | 16252 | (3R,5S)-3-benzyl-5-(hydroxymethyl)dihydro-2(3H)-furanone | C12H14O3 | 详情 | 详情 | |
| (XVI) | 16253 | [(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]methyl trifluoromethanesulfonate | C13H13F3O5S | 详情 | 详情 | |
| (XVII) | 16254 | tert-butyl (3S)-4-[[(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]methyl]-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | C26H39N3O5 | 详情 | 详情 | |
| (XVIII) | 16255 | tert-butyl (3S)-4-[(2S,4R)-5-amino-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | C26H42N4O5 | 详情 | 详情 | |
| (XIX) | 16256 | tert-butyl (3S)-4-((2S,4R)-5-amino-4-benzyl-2-[[tert-butyl(dimethyl)silyl]oxy]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C32H56N4O5Si | 详情 | 详情 | |
| (XX) | 16257 | tert-butyl (3S)-4-((2S,4R)-4-benzyl-2-[[tert-butyl(dimethyl)silyl]oxy]-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C41H64N4O6Si | 详情 | 详情 | |
| (XXI) | 16258 | tert-butyl (3S)-4-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C35H50N4O6 | 详情 | 详情 |
合成路线3
4) The condensation of the chiral piperazine (VII) with (S)-(+)-glycicyl 3-nitrobenzenesulfonate (XXII) by means of diisopropylethylamine in DMF [or with (S)-glycidol (XXIII), tosyl chloride and NaH] gives the epoxide (XXIV), which is condensed with the propionamide (IV) by means of butyllithium in THF, yielding the protected hydroxyamide (XXV). The deprotection of (XXV) with aqueous HCl affords the dihydroxy-diamide (VIII), already obtained, which is finally alkylated with 3-(chloromethyl)pyridine (IX) as before.
| 【1】 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600. |
| 【2】 Askin, D.; Reider, P.; Rossen, K.; Varsolona, R.J.; Wells, K.M. (Merck & Co., Inc.); Process for making HIV protease inhibitors. WO 9502583 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 16241 | 1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-3-phenyl-1-propanone | C21H23NO2 | 详情 | 详情 | |
| (VII) | 16244 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | 150323-35-6 | C14H27N3O3 | 详情 | 详情 |
| (VIII) | 16245 | (2S)-1-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-N-(tert-butyl)-2-piperazinecarboxamide | C30H42N4O4 | 详情 | 详情 | |
| (IX) | 15793 | 3-(Chloromethyl)pyridine | 3099-31-8 | C6H6ClN | 详情 | 详情 |
| (XXII) | 16259 | (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate | 115314-14-2 | C9H9NO6S | 详情 | 详情 |
| (XXIII) | 16260 | (R)-(+)-Glycidol; (2R)-Oxiranemethanol; (2R)oxiranylmethanol | 57044-25-4 | C3H6O2 | 详情 | 详情 |
| (XXIV) | 16261 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]-4-[(2R)oxiranylmethyl]tetrahydro-1(2H)-pyrazinecarboxylate | C17H31N3O4 | 详情 | 详情 | |
| (XXV) | 16262 | tert-butyl (3S)-4-[(2S,4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C38H54N4O6 | 详情 | 详情 |
合成路线4
5) The double bond of the pentenylamide (X) (as obtained in Scheme 1) is oxidized with OsO4 and N-methylmorpholine N-oxide in tert-butanol/water to give the 4(R,S),5-dihydroxy-compound (XXVI), which is esterified selectively with methanesulfonyl chloride, yielding the terminal monomesylate (XXVII). The condensation of (XXVII) with the chiral piperazine (VII) by means of K2CO3 in hot isopropanol yields the condensation product (XXVIII) with the (R,S)-configuration at the 4-OH group. The optical resolution of this 4-OH group with (S)-(+)-camphosulfonic acid affords the protected hydroxy-amide (XXV), already obtained in Scheme 19918303a.
| 【1】 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600. |
| 【2】 Vacca, J.P.; Guare, J.P.; Dorsey, B.D.; Holloway, M.K.; Hungate, R.W. (Merck & Co., Inc.); HIV protease inhibitors in pharmaceutical combinations for the treatment of AIDS. EP 0617968; JP 1996508496; WO 9422480 . |
| 【3】 Vacca, J.P.; Dorsey, B.D.; Guare, J.P.; Holloway, M.K.; Hungate, R.W.; Levin, R.B. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0696277; JP 1996509980; US 5413999; WO 9426717 . |
| 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) | 16244 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | 150323-35-6 | C14H27N3O3 | 详情 | 详情 |
| (X) | 16247 | (2S)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-4-penten-1-one | C24H27NO2 | 详情 | 详情 | |
| (XXV) | 16262 | tert-butyl (3S)-4-[(2S,4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C38H54N4O6 | 详情 | 详情 | |
| (XXVI) | 16263 | (2R)-1-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-2-benzyl-4,5-dihydroxy-1-pentanone | C24H29NO4 | 详情 | 详情 | |
| (XXVII) | 16264 | (4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl methanesulfonate | C25H31NO6S | 详情 | 详情 | |
| (XXVIII) | 16265 | tert-butyl (3S)-4-[(4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate | C38H54N4O6 | 详情 | 详情 |
合成路线5
6) The chiral piperazine (VII) can be obtained by several different ways: 6a) The sequential protection of piperazine-2(S)-carboxylic acid (XXIX) gives 1-(benzyloxycarbonyl)-4-(tert-butoxycarbonyl)piperazine-2(S)-carboxylic acid (XXX), which is condensed with tert-butylamine by means of EDC and HOBt to afford the tert-butylamide (XXXI). Finally, this compound is selectively deprotected by hydrogenation with H2 over Pd/C in methanol, yielding the chiral piperazine (VII). 6b) The partial hydrogenation of N-tert-butylpyrazine-2-carboxamide (XXXII) with H2 over Pd/C gives the tetrahydro derivative (XXXIII), which is sequentially protected as usual to the 1-(benzyloxycarbonyl)-4-(tert-butoxycarbonyl)-1,4,5,6-tetrahydropyrazin e -2-carboxamide (XXXIV). Finally, this compound is hydrogenated using the chiral catalyst [R-BINAP(COD)Rh]OTf to afford the chiral piperazine (XXXI), already obtained. 6c) The N-tert-butylpyrazine-2-carboxamide (XXXII) is fully reduced with H2 over Pd/C in propanol, giving the racemic N-tert-butylpiperazine-2-carboxamide (XXXV), which is submitted to optical resolution with (S)-(+)-camphosulfonic acid, yielding the (S)-isomer (XXXVI), which is then selectively protected with tert-butoxycarbonyl anhydride to give the desired chiral amide (VII).
| 【1】 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600. |
| 【2】 Rossen, K.; Weissman, S.A.; Sager, J.; Reamer, R.A.; Askin, D.; Volante, R.P.; Reider, P.J.; Asymmetric hydrogenation of tetrahydropyrazines: Synthesis of (S)-piperazine-2-tert-butylcarboxamide, an intermediate in the preparation of the HIV protease inhibitor indinavir. Tetrahedron Lett 1995, 36, 36, 6419-22. |
| 【3】 Vacca, J.P.; Guare, J.P.; Dorsey, B.D.; Holloway, M.K.; Hungate, R.W. (Merck & Co., Inc.); HIV protease inhibitors in pharmaceutical combinations for the treatment of AIDS. EP 0617968; JP 1996508496; WO 9422480 . |
| 【4】 Vacca, J.P.; Dorsey, B.D.; Guare, J.P.; Holloway, M.K.; Hungate, R.W.; Levin, R.B. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0696277; JP 1996509980; US 5413999; WO 9426717 . |
| 【5】 Askin, D.; Reider, P.; Rossen, K.; Varsolona, R.J.; Wells, K.M. (Merck & Co., Inc.); Process for making HIV protease inhibitors. WO 9502583 . |
| 【6】 Verhoeven, T.R.; Roberts, E.F.; Senanayake, C.H.; Ryan, K.M. (Merck & Co., Inc.); Regiospecific processes to make cis-1-amino-2-alkanol from diol or halohydrin. US 5449830 . |
| 【7】 Dorsey, B.D.; Levin, R.B.; McDaniel, S.L.; et al.; L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor. J Med Chem 1994, 37, 21, 3443-51. |
| 【8】 Askin, D.; Eng, K.K.; Rossen, K.; Purick, R.M.; Wells, K.M.; Volante, R.P.; Reider, P.J.; Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524. Tetrahedron Lett 1994, 35, 5, 673-6. |
| 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) | 16244 | tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate | 150323-35-6 | C14H27N3O3 | 详情 | 详情 |
| (XXIX) | 16266 | (2S)-hexahydro-2-pyrazinecarboxylic acid; (S)-Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
| (XXX) | 16267 | (2S)-1-[(benzyloxy)carbonyl]-4-(tert-butoxycarbonyl)hexahydro-2-pyrazinecarboxylic acid | C18H24N2O6 | 详情 | 详情 | |
| (XXXI) | 16268 | 1-benzyl 4-(tert-butyl) (2S)-2-[(tert-butylamino)carbonyl]tetrahydro-1,4-pyrazinedicarboxylate | C22H33N3O5 | 详情 | 详情 | |
| (XXXII) | 16269 | N-(tert-butyl)-2-pyrazinecarboxamide | 121885-10-7 | C9H13N3O | 详情 | 详情 |
| (XXXIII) | 16270 | N-(tert-butyl)-1,4,5,6-tetrahydro-2-pyrazinecarboxamide | C9H17N3O | 详情 | 详情 | |
| (XXXIV) | 16271 | 4-benzyl 1-(tert-butyl) 5-[(tert-butylamino)carbonyl]-2,3-dihydro-1,4-pyrazinedicarboxylate | C22H31N3O5 | 详情 | 详情 | |
| (XXXV) | 16272 | N-(tert-butyl)-2-piperazinecarboxamide; Piperazine-2-carboxylic acid tert-butylamide | C9H19N3O | 详情 | 详情 | |
| (XXXVI) | 16273 | (2S)-N-(tert-butyl)hexahydro-2-pyrazinecarboxamide | C9H19N3O | 详情 | 详情 |