【结 构 式】 |
【分子编号】56272 【品名】(3R)-3-amino-3-phenylpropanoic acid 【CA登记号】 |
【 分 子 式 】C9H11NO2 【 分 子 量 】165.19188 【元素组成】C 65.44% H 6.71% N 8.48% O 19.37% |
合成路线1
该中间体在本合成路线中的序号:(XIII)An alternative synthesis starting from the chiral precursor N-Boc-(R)-phenylglycine (IX) was reported. Borane reduction of (IX) provided the N-Boc aminoalcohol (X), which was activated as the mesylate (XI) by reaction with methanesulfonyl chloride in pyridine, yielding (XI). Displacement of the mesylate group of (XI) with NaCN furnished the Boc-aminonitrile (XII). Hydrolysis of the nitrile group of (XII) with concomitant N-Boc group cleavage under acidic conditions gave aminoacid (XIII). This was reduced to amino alcohol (XIV) using borane in THF. Eschweiler-Clarke methylation of aminoalcohol (XIV) yielded the dimethyl amine (XV). This was finally condensed with 1-fluoronaphthalene (VIII) to produce the title naphthyl ether. The [14C]-labeled compound was similarly prepared employing 14C-sodium cyanide.
【1】 Wheeler, W.J.; O'Bannon, D.D.; A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer. J Label Compd Radiopharm 1992, 31, 4, 305. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIII) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
(IX) | 22613 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoic acid | 2900-27-8 | C13H17NO4 | 详情 | 详情 |
(X) | 59225 | (R)-N-(tert-Butoxycarbonyl)-phenylglycinol; N-t-BOC-D-phenylglycinol | 102089-74-7 | C13H19NO3 | 详情 | 详情 |
(XI) | 59226 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-phenylethyl methanesulfonate | C14H21NO5S | 详情 | 详情 | |
(XII) | 59227 | tert-butyl (1S)-2-cyano-1-phenylethylcarbamate | C14H18N2O2 | 详情 | 详情 | |
(XIII) | 56272 | (3R)-3-amino-3-phenylpropanoic acid | C9H11NO2 | 详情 | 详情 | |
(XIV) | 59228 | (R)-3-Amino-3-phenylpropan-1-ol | C9H13NO | 详情 | 详情 | |
(XV) | 59229 | (3S)-3-(dimethylamino)-3-phenyl-1-propanol | C11H17NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(III)The title compound was synthesized within a combinatorial library on a Wang polystyrene resin. Attachment of N-Fmoc-(R)-beta-phenylalanine (I) to the solid support was achieved via activation with 2,6-dichlorobenzoyl chloride to afford the aminoacid-bound resin (II). After conventional Fmoc group deprotection with piperidine in DMF, the resultant amine resin (III) was acylated with 5-bromo-2-methoxybenzenesulfonyl chloride (IV) yielding sulfonamide (V). Mitsunobu coupling between aryl bromide (V) and 3-nitrobenzeneboronic acid (VI) gave rise to the biphenyl derivative (VII). Reduction of the nitro group of (VII) to the corresponding aniline (VIII) was then performed by treatment with stannous chloride in N-methylpyrrolidone. Alternatively, the aminobiphenyl resin (VIII) was directly prepared by coupling between aryl bromide (V) and 3-aminobenzeneboronic acid (IX). Reaction of amine (VIII) with p-nitrophenyl chloroformate (X) produced the nitrophenyl carbamate resin (IX), which was further reacted with 2-aminobenzimidazole (XII) to furnish urea (XIII). Final resin cleavage was effected by treatment with trifluoroacetic acid in CH2Cl2.
【1】 Gerdes, C.; Albers, M.; Schmidt, D.; Stelte-Ludwig, B.; Bruggemeier, U.; Vaupel, A.; Harter, M.; Urbahns, K.; Biphenyls as potent vitronectin receptor antagonists. Bioorg Med Chem Lett 2002, 12, 2, 205. |
【2】 Schmidt, D.; Urbahns, K.; Gerdes, C.; Keldenich, J.; Härter, M.; Stahl, E.; Albers, M.; Vaupel, A.; Stelte-Ludwig, B.; Brüggemeier, U.; Lustig, K. (Bayer AG); New biphenyl and biphenyl-analogous cpds. as integrin antagonists. EP 1140809; JP 2002532465; US 6420396; WO 0035864 . |
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),(II) | 56271 | Fmoc-(R)-3-amino-3-phenylpropionic acid | C24H21NO4 | 详情 | 详情 | |
(III) | 56272 | (3R)-3-amino-3-phenylpropanoic acid | C9H11NO2 | 详情 | 详情 | |
(IV) | 56273 | 5-Bromo-2-methoxybenzenesulfonyl chloride | 23095-05-8 | C7H6BrClO3S | 详情 | 详情 |
(V) | 56274 | (3R)-3-{[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-3-phenylpropanoic acid | C16H16BrNO5S | 详情 | 详情 | |
(VI) | 40934 | 3-nitrophenylboronic acid | 13331-27-6 | C6H6BNO4 | 详情 | 详情 |
(VII) | 56275 | (3R)-3-{[(4-methoxy-3'-nitro[1,1'-biphenyl]-3-yl)sulfonyl]amino}-3-phenylpropanoic acid | C22H20N2O7S | 详情 | 详情 | |
(VIII) | 56276 | (3-Aminophenyl)dihydroxyborane; 3-Aminobenzeneboronic acid; 3-Aminophenylboronic acid | 30418-59-8 | C22H22N2O5S | 详情 | 详情 |
(IX) | 56277 | 3-aminophenylboronic acid | C6H8BNO2 | 详情 | 详情 | |
(X) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
(XI) | 56278 | (3R)-3-{[(4-methoxy-3'-{[(4-nitrophenoxy)carbonyl]amino}[1,1'-biphenyl]-3-yl)sulfonyl]amino}-3-phenylpropanoic acid | C29H25N3O9S | 详情 | 详情 | |
(XII) | 48437 | 2-Aminobenzimidazole; 2-Amino-1H-benzimidazol; 1H-Benzimidazol-2-amine; 2-Benzimidazolamine | 934-32-7 | C7H7N3 | 详情 | 详情 |
(XIII) | 56279 | (3R)-3-{[(3'-{[(1H-benzimidazol-2-ylamino)carbonyl]amino}-4-methoxy[1,1'-biphenyl]-3-yl)sulfonyl]amino}-3-phenylpropanoic acid | C30H27N5O6S | 详情 | 详情 |