(alphaS)-alpha-[[(1R)-2-Hydroxy-1-phenylethyl]amino]-tricyclo[3.3.1.1(3,7)]decane-1-acetonitrile -Drug Synthesis Database

【结构式】

【分子编号】65696

【品名】(alphaS)-alpha-[[(1R)-2-Hydroxy-1-phenylethyl]amino]-tricyclo[3.3.1.1(3,7)]decane-1-acetonitrile

【CA登记号】361441-95-4

【分子式】C₂₀H₂₆N₂O

【分子量】310.43932

【元素组成】C 77.38% H 8.44% N 9.02% O 5.15%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XX)

The intermediate (S)-adamantylglycine (I) can be prepared as follows. Reduction of adamantane-1-carboxylic acid (XVI) using LiAlH4 in THF gives the primary alcohol (XVII), which is oxidized to aldehyde (XVIII) under Swern conditions. Adamantane-1-carbaldehyde (XVIII) is then condensed with (R)-phenylglycinol (XIX) and KCN in the presence of NaHSO3 to yield the chiral aminonitrile (XX). After acidic hydrolysis of nitrile (XX) to the corresponding amino acid (XXI), the chiral auxiliary group is removed by hydrogenolysis over Pearlman’s catalyst to furnish intermediate (I) (1, 6). Scheme 2.

参考文献中间体

合成目标

【1】 Robl, J.A., Sulsky, R.B., Betebenner, D.A., Magnin, D.R., Hamann, L.G., Augeri, D.J. (Bristol-Myers Squibb Co.). Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method. EP 1261586, JP 2003531118, US 6395767, WO 0168603.
【6】 Augeri, D.J., Robl, J.A., Betebenner, D.A. et al. Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005, 48(15): 5025-37.

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)	65644			C₃₅H₄₁INOPSSi	详情	详情
(XVI)	65693	1-Adamantanecarboxylic acid; Adamantane-1-carboxylic acid; Tricyclo[3.3.1.1(3,7)]decan-1-Carboxylic acid	828-51-3	C₁₁H₁₆O₂	详情	详情
(XVII)	65694	1-Adamantanemethanol; 1-(Hydroxymethyl)adamantane; 1-Tricyclo[3.3.1.1(3,7)]decanemethanol	770-71-8	C₁₁H₁₈O	详情	详情
(XVIII)	65695	1-Adamantylcarboxaldehyde; Tricyclo[3.3.1.1(3,7)]decane-1-carboxaldehyde; 1-Formyladamantane	2094-74-8	C₁₁H₁₆O	详情	详情
(XIX)	14376	(2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol	56613-80-0	C₈H₁₁NO	详情	详情
(XX)	65696	(alphaS)-alpha-[[(1R)-2-Hydroxy-1-phenylethyl]amino]-tricyclo[3.3.1.1(3,7)]decane-1-acetonitrile	361441-95-4	C₂₀H₂₆N₂O	详情	详情
(XXI)	65697			C₂₀H₂₇NO₃	详情	详情

Extended Information