(3S)-3-methylmorpholine -Drug Synthesis Database

【结构式】

【分子编号】55061

【品名】(3S)-3-methylmorpholine

【CA登记号】

【分子式】C₅H₁₁NO

【分子量】101.14848

【元素组成】C 59.37% H 10.96% N 13.85% O 15.82%

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)

Condensation of L-alaninol (I) with benzaldehyde produced imine (II), which was further reduced to the N-benzyl amine (III) by means of NaBH4. Subsequent acylation of N-benzyl alaninol (III) with chloroacetyl chloride (IV) provided the chloroacetamide (V). This was subjected to intramolecular cyclization in the presence of NaH to afford morpholinone (VI). Lactam (VI) reduction employing LiAlH4 furnished the substituted morpholine (VII). The N-benzyl group of (VII) was then removed by hydrogenation in the presence of Pd/C, yielding (S)-3-methylmorpholine (VIII).

参考文献中间体

合成目标

【1】 Powers, J.P. (Tularik Inc.); Arylsulfonic acid salts of pyrimidine-based antiviral agents. US 6410726; WO 0151485 .

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)	14341	L-Alaninol; (2S)-2-Amino-1-propanol; L-(+)-Alaninol	2749-11-3	C₃H₉NO	详情	详情
(II)	55056	(2S)-2-{[(E)-phenylmethylidene]amino}-1-propanol		C₁₀H₁₃NO	详情	详情
(III)	55057	(2S)-2-(benzylamino)-1-propanol		C₁₀H₁₅NO	详情	详情
(IV)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(V)	55058	N-benzyl-2-chloro-N-[(1S)-2-hydroxy-1-methylethyl]acetamide		C₁₂H₁₆ClNO₂	详情	详情
(VI)	55059	(5S)-4-benzyl-5-methyl-3-morpholinone		C₁₂H₁₅NO₂	详情	详情
(VII)	55060	(3S)-4-benzyl-3-methylmorpholine		C₁₂H₁₇NO	详情	详情
(VIII)	55061	(3S)-3-methylmorpholine		C₅H₁₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The dihydroxypyrimidine (IX) was converted to the 2-chloro derivative (XI) by chlorination with phosphoryl chloride and N,N-dimethylaniline, followed by treatment of the resultant dichloropyrimidine (X) with NaOAc/HOAc in aqueous EtOH. Nucleophilic displacement in chloropyrimidine (XI) with (S)-3-methylmorpholine (VIII) furnished adduct (XII). Subsequent chlorination of (XII) in hot POCl3 gave rise to the chloropyrimidine (XIII). This was then displaced with imidazole (XIV) to produce the target imidazolyl pyrimidine, which was isolated as the benzenesulfonate salt.

参考文献中间体

合成目标

【1】 Powers, J.P. (Tularik Inc.); Arylsulfonic acid salts of pyrimidine-based antiviral agents. US 6410726; WO 0151485 .

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)	55061	(3S)-3-methylmorpholine		C₅H₁₁NO	详情	详情
(IX)	55062	6-Methyl-5-nitropyrimidine-2,4-diol; 6-Methyl-5-nitrouracil		C₅H₅N₃O₄	详情	详情
(X)	55063	2,4-dichloro-6-methyl-5-nitropyrimidine		C₅H₃Cl₂N₃O₂	详情	详情
(XI)	55064	2-chloro-6-methyl-5-nitro-4-pyrimidinol		C₅H₄ClN₃O₃	详情	详情
(XII)	55065	6-methyl-2-[(3S)-3-methylmorpholinyl]-5-nitro-4-pyrimidinol		C₁₀H₁₄N₄O₄	详情	详情
(XIII)	55066	(3S)-4-(4-chloro-6-methyl-5-nitro-2-pyrimidinyl)-3-methylmorpholine		C₁₀H₁₃ClN₄O₃	详情	详情
(XIV)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情

Extended Information