(1S,5R,7R)-10,10-dimethyl-4-octanoyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione -Drug Synthesis Database

【结构式】

【分子编号】58243

【品名】(1S,5R,7R)-10,10-dimethyl-4-octanoyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione

【CA登记号】

【分子式】C₁₈H₃₁NO₃S

【分子量】341.51508

【元素组成】C 63.31% H 9.15% N 4.1% O 14.05% S 9.39%

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：(III)

The acylation of (-)-2,10-camphorsultam (II) with octanoyl chloride (I) provides the N-octanoyl sultam (III). Diastereoselective alkylation of the lithium enolate of (III) with allyl bromide (IV) gives rise to the (2S)-2-propenoyloctanoyl sultam (V). Hydrolysis of the N-acyl sultam (V) to furnish acid (VI) is then effected by treatment with hydrogen peroxide-tetrabutylammonium hydroxide. Finally, catalytic hydrogenation of the unsaturated acid (VI) in the presence of either Pd/C or Pt/C yields the required (R)-2-propyloctanoic acid. Alternatively, the title compound is obtained by hydrogenation of the N-acyl sultam (V) to the saturated derivative (VII), followed by hydrolytic removal of the camphorsultam moiety.

参考文献中间体

合成目标

【1】 Hasegawa, T.; Kawanaka, Y.; Kasamatsu, E.; Iguchi, Y.; Yonekawa, Y.; Okamoto, M.; Ohta, C.; Hashimoto, S.; Ohuchida, S.; Process development of ONO-2506: A therapeutic agent for stroke and Alzheimer's disease. Org Process Res Dev 2003, 7, 2, 168.
【2】 Hasegawa, T.; Yamamoto, H.; A practical synthesis of optically active (R)-2-propyloctanoic acid: Therapeutic agent for Alzheimer's disease. Bull Chem Soc Jpn 2000, 73, 2, 423.
【3】 Hasegawa, T.; Yamamoto, H.; A practical removal method of camphorsultam. Synlett 1998, 8, 882.
【4】 Yamamoto, H. (Ono Pharmaceutical Co., Ltd.); Novel intermediates and processes for the preparation of optically active octanoic acid derivs.. EP 1078921; US 6333415; WO 9958513 .

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)	11123	Octanoyl chloride; n-Caprylyl chloride;Capryloyl chloride	111-64-8	C₈H₁₅ClO	详情	详情
(II)	58242	(1S,5R,7R)-10,10-dimethyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₁₀H₁₇NO₂S	详情	详情
(III)	58243	(1S,5R,7R)-10,10-dimethyl-4-octanoyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₁₈H₃₁NO₃S	详情	详情
(IV)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(V)	58244	(1S,5R,7R)-4-[(2S)-2-hexyl-4-pentenoyl]-10,10-dimethyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₂₁H₃₅NO₃S	详情	详情
(VI)	58245	(1S,5R,7R)-10,10-dimethyl-4-[(2R)-2-propyloctanoyl]-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₂₁H₃₇NO₃S	详情	详情
(VII)	58246	(2S)-2-hexyl-4-pentenoic acid		C₁₁H₂₀O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

In a related procedure, the N-octanoyl sultam (I) is alkylated by propargyl bromide (II) to produce (III). Hydrolysis of (III) by means of hydrogen peroxide-tetrabutylammonium hydroxide or lithium hydroxide-hydrogen peroxide furnishes acid (IV). Then, catalytic hydrogenation of the propargyloctanoic acid (IV) in the presence of either Pd/C or Pt/C provides the title compound.

参考文献中间体

合成目标

【1】 Hasegawa, T.; Yamamoto, H.; A practical synthesis of optically active (R)-2-propyloctanoic acid: Therapeutic agent for Alzheimer's disease. Bull Chem Soc Jpn 2000, 73, 2, 423.
【2】 Yamamoto, H. (Ono Pharmaceutical Co., Ltd.); Novel intermediates and processes for the preparation of optically active octanoic acid derivs.. EP 1078921; US 6333415; WO 9958513 .
【3】 Iguchi, Y.; Yamaguchi, K.; Toda, N. (Ono Pharmaceutical Co., Ltd.; Tokyo Kasei Kogyo Co., Ltd.); Process for the preparation of (2R)-2-propyloctanoic acid. EP 1153910; WO 0048982 .

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)	58243	(1S,5R,7R)-10,10-dimethyl-4-octanoyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₁₈H₃₁NO₃S	详情	详情
(II)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(III)	58247	(1S,5R,7R)-4-[(2S)-2-hexyl-4-pentynoyl]-10,10-dimethyl-3lambda~6~-thia-4-azatricyclo[5.2.1.0~1,5~]decane-3,3-dione		C₂₁H₃₃NO₃S	详情	详情
(IV)	58248	(2S)-2-hexyl-4-pentynoic acid		C₁₁H₁₈O₂	详情	详情

Extended Information