(2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】62803

【品名】(2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylic acid

【CA登记号】

【分子式】C₃₅H₄₀N₂O₅

【分子量】568.71308

【元素组成】C 73.92% H 7.09% N 4.93% O 14.07%

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：(IX)

Esterification of N-benzyloxycarbonyl-D-proline (I) with MeOH in the presence of EDC, followed by deprotection of the resultant N-Cbz amino ester (II) with H2 and Pd(OH)2 leads to D-proline methyl ester (III). Subsequent coupling of (III) with N-benzyloxycarbonyl-O-t-butyl-L-4-trans-hydroxyproline (IV) yields the protected dipeptide (V). After removal of the N-benzyloxycarbonyl group of (V) by catalytic hydrogenolysis, the free amine (VI) is acylated by 3,3,3-triphenylpropionic acid (VII), producing amide (VIII). The methyl ester group of (VIII) is then hydrolyzed under alkaline conditions to furnish acid (IX).

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	CAS号	分子式	供应商	用于合成
(I)	17005	(2R)-1-[(benzyloxy)carbonyl]tetrahydro-1H-pyrrole-2-carboxylic acid		C₁₃H₁₅NO₄	详情	详情
(II)	62798	1-benzyl 2-methyl (2R)-1,2-pyrrolidinedicarboxylate		C₁₄H₁₇NO₄	详情	详情
(III)	36811	methyl (2R)-2-pyrrolidinecarboxylate		C₆H₁₁NO₂	详情	详情
(IV)	62799	(2S,4R)-1-[(benzyloxy)carbonyl]-4-(tert-butoxy)-2-pyrrolidinecarboxylic acid		C₁₇H₂₃NO₅	详情	详情
(V)	62800	benzyl (2S,4R)-4-(tert-butoxy)-2-{[(2R)-2-(methoxycarbonyl)pyrrolidinyl]carbonyl}-1-pyrrolidinecarboxylate		C₂₃H₃₂N₂O₆	详情	详情
(VI)	62801	methyl (2R)-1-{[(2S,4R)-4-(tert-butoxy)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylate		C₁₅H₂₆N₂O₄	详情	详情
(VII)	57640	3,3,3-Triphenylpropionic acid; Tritylacetic acid	900-91-4	C₂₁H₁₈O₂	详情	详情
(VIII)	62802	methyl (2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylate		C₃₆H₄₂N₂O₅	详情	详情
(IX)	62803	(2R)-1-{[(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidinyl]carbonyl}-2-pyrrolidinecarboxylic acid		C₃₅H₄₀N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

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