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【结 构 式】

【分子编号】38647

【品名】methyl (2S)-2-[[(5-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino][1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate

【CA登记号】

【 分 子 式 】C46H51N3O5S2

【 分 子 量 】790.06016

【元素组成】C 69.93% H 6.51% N 5.32% O 10.13% S 8.12%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IX)

The condensation of 2-bromo-4-nitrotoluene (I) with phenylboronic acid (II) by means of Pd(OAc)2 in aqueous acetone gives the biphenyl (III), which is oxidized with KMnO4 in aqueous pyridine yielding the biphenyl-2-carboxylic acid (IV). The condensation of (IV) with L-methionine methyl ester (V) by means of EDC and HOBT affords the amide (VI), which is reduced with SnCl2 to give the 5-aminobiphenyl derivative (VII). The reductocondensation of (VII) with N-(tert-butoxycarbonyl)-S-trityl-L-cysteinal (VIII) by means of NaBH3CN affords the secondary amine (IX), which is finally deprotected with HgCl2 and H2S in methanol to furnish the target ester.

1 Fossum, R.D.; Marugan, J.J.; Vogt, A.; Qian, Y.; Sebti, S.M.; Hamilton, A.D.; Probing the hydrophobic pocket of farnesyltransferase: Aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors. Bioorg Med Chem 1999, 7, 12, 3011.
2 Sebti, S.; Hamilton, A. (University of Pittsburgh); Inhibitors of prenyl transferases. JP 1998512266; WO 9621456 .
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) 38642 2-bromo-1-methyl-4-nitrobenzene 7745-93-9 C7H6BrNO2 详情 详情
(II) 16593 Phenylboronic acid;Benzeneboronic acid;Phenylboron dihydroxide 98-80-6 C6H7BO2 详情 详情
(III) 38643 2-methyl-5-nitro-1,1'-biphenyl C13H11NO2 详情 详情
(IV) 38644 5-nitro[1,1'-biphenyl]-2-carboxylic acid C13H9NO4 详情 详情
(V) 17950 D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride 21691-49-6 C6H13NO2S 详情 详情
(VI) 38645 methyl (2S)-4-(methylsulfanyl)-2-[[(5-nitro[1,1'-biphenyl]-2-yl)carbonyl]amino]butanoate C19H20N2O5S 详情 详情
(VII) 38656 2,2,2-trichloroethyl (3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-piperidinecarboxylate C9H14Cl3NO5 详情 详情
(VIII) 17953 tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate C27H29NO3S 详情 详情
(IX) 38647 methyl (2S)-2-[[(5-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino][1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate C46H51N3O5S2 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 condensation of 2-bromo-4-nitrotoluene (I) with phenylboronic acid (II) by means of Pd(OAc)2 in aqueous acetone gives the biphenyl (III), which is oxidized with KMnO4 in aqueous pyridine yielding the biphenyl-2-carboxylic acid (IV). The condensation of (IV) with L-methionine methyl ester (V) by means of EDC and HOBT affords the amide (VI), which is reduced with SnCl2 to give the 5-aminobiphenyl derivative (VII). The reductocondensation of (VII) with N-(tert-butoxycarbonyl)-S-trityl-L-cysteinal (VIII) by means of NaBH3CN affords the secondary amine (IX), which is finally deprotected and hydrolyzed first with LiOH and THF and then with TFA and Et3SiH in dichloromethane to furnish the target free acid.

1 Fossum, R.D.; Marugan, J.J.; Vogt, A.; Qian, Y.; Sebti, S.M.; Hamilton, A.D.; Probing the hydrophobic pocket of farnesyltransferase: Aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors. Bioorg Med Chem 1999, 7, 12, 3011.
2 Sebti, S.; Hamilton, A. (University of Pittsburgh); Inhibitors of prenyl transferases. JP 1998512266; WO 9621456 .
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) 38642 2-bromo-1-methyl-4-nitrobenzene 7745-93-9 C7H6BrNO2 详情 详情
(II) 16593 Phenylboronic acid;Benzeneboronic acid;Phenylboron dihydroxide 98-80-6 C6H7BO2 详情 详情
(III) 38643 2-methyl-5-nitro-1,1'-biphenyl C13H11NO2 详情 详情
(IV) 38644 5-nitro[1,1'-biphenyl]-2-carboxylic acid C13H9NO4 详情 详情
(V) 17950 D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride 21691-49-6 C6H13NO2S 详情 详情
(VI) 38645 methyl (2S)-4-(methylsulfanyl)-2-[[(5-nitro[1,1'-biphenyl]-2-yl)carbonyl]amino]butanoate C19H20N2O5S 详情 详情
(VII) 38656 2,2,2-trichloroethyl (3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-1-piperidinecarboxylate C9H14Cl3NO5 详情 详情
(VIII) 17953 tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate C27H29NO3S 详情 详情
(IX) 38647 methyl (2S)-2-[[(5-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino][1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate C46H51N3O5S2 详情 详情
Extended Information