tert-butyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】57643

【品名】tert-butyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₁H₂₂N₂O₂

【分子量】214.30796

【元素组成】C 61.65% H 10.35% N 13.07% O 14.93%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

Coupling between ethyl 3-aminopropionate (I) and N-Boc-glycine (II) by means of EDC and HOBt affords the protected dipeptide (III). After acidic Boc group cleavage in (III), the N-deprotected dipeptide (IV) is acylated by 3,3,3-triphenylpropionic acid (V) to produce amide (VI). Saponification of the ethyl ester group of (VI) yields acid (VII). This is coupled with (R)-1-Boc-3-(aminomethyl)piperidine (VIII) to afford amide (IX), which is further subjected to acidic N-Boc group cleavage. The resultant piperidine derivative (X) is then reductively condensed with cyclohexanecarboxaldehyde (XI) in the presence of NaBH(OAc)3 to furnish the title compound.

参考文献中间体

合成目标

【1】 Kimura, T.; Noguchi, K.; Otake, N.; Uchiyama, M.; Naya, A.; Sagara, Y.; Numazawa, T.; Fujikawa, T. (Banyu Pharmaceutical Co., Ltd.); Novel amide derivs.. EP 1213281; WO 0107406 .

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)	17639	beta-Alanine, ethyl ester; ethyl 3-aminopropanoate	924-73-2	C₅H₁₁NO₂	详情	详情
(II)	18066	N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid	4530-20-5	C₇H₁₃NO₄	详情	详情
(III)	57638	ethyl 3-({2-[(tert-butoxycarbonyl)amino]acetyl}amino)propanoate		C₁₂H₂₂N₂O₅	详情	详情
(IV)	57639	ethyl 3-[(2-aminoacetyl)amino]propanoate		C₇H₁₄N₂O₃	详情	详情
(V)	57640	3,3,3-Triphenylpropionic acid; Tritylacetic acid	900-91-4	C₂₁H₁₈O₂	详情	详情
(VI)	57641	ethyl 3-({2-[(3,3,3-triphenylpropanoyl)amino]acetyl}amino)propanoate		C₂₈H₃₀N₂O₄	详情	详情
(VII)	57642	N-{2-[(3,3,3-triphenylpropanoyl)amino]acetyl}-beta-alanine		C₂₆H₂₆N₂O₄	详情	详情
(VIII)	57643	tert-butyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate		C₁₁H₂₂N₂O₂	详情	详情
(IX)	57644	tert-butyl (3R)-3-({[3-({2-[(3,3,3-triphenylpropanoyl)amino]acetyl}amino)propanoyl]amino}methyl)-1-piperidinecarboxylate		C₃₇H₄₆N₄O₅	详情	详情
(X)	57645	N-{2-oxo-2-[(3-oxo-3-{[(3S)piperidinylmethyl]amino}propyl)amino]ethyl}-3,3,3-triphenylpropanamide		C₃₂H₃₈N₄O₃	详情	详情
(XI)	33694	cyclohexanecarbaldehyde	2043-61-0	C₇H₁₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Coupling of acid (IX) with (R)-3-(aminomethyl)-1-Boc-piperidine (X) gives the triamide (XI). Deprotection of both N-Boc and O-t-butyl groups of (XI) with trifluoroacetic acid affords (XII). Finally, reductive alkylation of piperidine (XII) with propionaldehyde in the presence of NaBH3CN/ZnCl2 provides the target compound.

参考文献中间体

合成目标

【1】 Sagara, Y.; Kimura, T.; Fujikawa, T.; Noguchi, K.; Ohtake, N.; Identification of novel muscarinic M3 selective antagonists with a conformationally restricted Hyp-Pro spacer. Bioorg Med Chem Lett 2003, 13, 1, 57.
【2】 Kimura, T.; Noguchi, K.; Otake, N.; Uchiyama, M.; Naya, A.; Sagara, Y.; Numazawa, T.; Fujikawa, T. (Banyu Pharmaceutical Co., Ltd.); Novel amide derivs.. EP 1213281; WO 0107406 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	62803	(2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylic acid	C₃₅H₄₀N₂O₅	详情	详情
(X)	57643	tert-butyl (3R)-3-(aminomethyl)-1-piperidinecarboxylate	C₁₁H₂₂N₂O₂	详情	详情
(XI)	62804	tert-butyl (3R)-3-({[((2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}pyrrolidinyl)carbonyl]amino}methyl)-1-piperidinecarboxylate	C₄₆H₆₀N₄O₆	详情	详情
(XII)	62805	(2R)-1-{[(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-N-[(3S)piperidinylmethyl]-2-pyrrolidinecarboxamide	C₃₇H₄₄N₄O₄	详情	详情

Extended Information