(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】40502

【品名】(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol

【CA登记号】116817-84-6

【分子式】C₉H₁₅NOS

【分子量】185.29024

【元素组成】C 58.34% H 8.16% N 7.56% O 8.63% S 17.31%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(IV)

Reaction of 2-acetylthiophene (I) with paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-1-propanone (II), which is enantioselectively reduced with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene to yield (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene and treated with oxalic acid.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907.
【2】 Staszak, M.A.; Staten, G.S.; Weigel, L.O. (Eli Lilly and Company); Chiral synthesis of 1-aryl-3-aminopropan-1-ols. CA 2042346; EP 0457559; JP 1992226948 .
【3】 Frazier, J.; Staszak, M.; Weigel, L.; Staten, G.; Deeter, J.; Asymmetric synthesis and absolute stereochemistry of LY248686. Tetrahedron Lett 1990, 31, 49, 7101.

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)	24490	1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene	88-15-3	C₆H₆OS	详情	详情
(II)	40500	3-(dimethylamino)-1-(2-thienyl)-1-propanone	13196-35-5	C₉H₁₃NOS	详情	详情
(III)	40501	(2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol	63957-11-9	C₁₉H₂₅NO	详情	详情
(IV)	40502	(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol	116817-84-6	C₉H₁₅NOS	详情	详情
(V)	40503	1-fluoronaphthalene	321-38-0	C₁₀H₇F	详情	详情
(VI)	40504	(3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine	132335-46-7	C₁₉H₂₁NOS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The ketone intermediate (II) can also be reduced with NaBH4 in ethanol to the racemic alcohol (VII), which is submitted to optical resolution with (S)-(+)-mandelic acid to provide the (S)-enantiomer (IV) already described.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907.
【2】 Berglund, R.A. (Eli Lilly and Company); Asymmetric synthesis. EP 0650965; JP 1995188065; US 5362886 .

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)	24490	1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene	88-15-3	C₆H₆OS	详情	详情
(II)	40500	3-(dimethylamino)-1-(2-thienyl)-1-propanone	13196-35-5	C₉H₁₃NOS	详情	详情
(IV)	40502	(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol	116817-84-6	C₉H₁₅NOS	详情	详情
(VII)	40515	3-(dimethylamino)-1-(2-thienyl)-1-propanol		C₉H₁₅NOS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The reaction of 2-acetylthiophene (I) with [14C]-paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-[3-14C]propan-1-one (II), which is enantioselectively reduced in toluene with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene to yield (S)-3-(dimethylamino)-1-(2-thienyl)-[3-14C]propan-1-ol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene.

参考文献中间体

合成目标

【1】 Wheeler, W.J.; Kuo, F.; Approaches to an asymmetric synthesis of duloxetine, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled analogs. Synthesis and Applications of Isotopically Labelled Compounds 1994, 597-603.
【2】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907.

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)	24490	1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene	88-15-3	C₆H₆OS	详情	详情
(II)	40500	3-(dimethylamino)-1-(2-thienyl)-1-propanone	13196-35-5	C₉H₁₃NOS	详情	详情
(III)	40501	(2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol	63957-11-9	C₁₉H₂₅NO	详情	详情
(IV)	40502	(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol	116817-84-6	C₉H₁₅NOS	详情	详情
(V)	40503	1-fluoronaphthalene	321-38-0	C₁₀H₇F	详情	详情
(VI)	40504	(3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine	132335-46-7	C₁₉H₂₁NOS	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The reaction of [carbonyl-14C]-2-acetylthiophene (I) with paraformaldehyde and dimethylamine in ethanol gives 3-(dimethylamino)-1-(2-thienyl)-[1-14C]propan-1-one (II), which is enantioselectively reduced with a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol (III) and LiAlH4 in toluene, yielding (S)-3-(dimethylamino)-1-(2-thienyl)[1-14C] propan-1-ol (IV). The condensation of (IV) with 1-fluoronaphthalene (V) by means of NaH in DMSO affords the corresponding naphthyl ether (VI), which is finally monodemethylated with 2,2,2-trichloroethyl chloroformate and Zn in toluene.

参考文献中间体

合成目标

【1】 Wheeler, W.J.; Kuo, F.; Approaches to an asymmetric synthesis of duloxetine, a mixed uptake inhibitor of serotonin and norepinephrine, and its C-14 labeled analogs. Synthesis and Applications of Isotopically Labelled Compounds 1994, 597-603.
【2】 Sorbera, L.A.; Castaner, R.M.; Castaner, J.; Duloxetine oxalate. Drugs Fut 2000, 25, 9, 907.

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)	24490	1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene	88-15-3	C₆H₆OS	详情	详情
(II)	40500	3-(dimethylamino)-1-(2-thienyl)-1-propanone	13196-35-5	C₉H₁₃NOS	详情	详情
(III)	40501	(2S,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanol	63957-11-9	C₁₉H₂₅NO	详情	详情
(IV)	40502	(1S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol	116817-84-6	C₉H₁₅NOS	详情	详情
(V)	40503	1-fluoronaphthalene	321-38-0	C₁₀H₇F	详情	详情
(VI)	40504	(3S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)-1-propanamine; N,N-dimethyl-N-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine	132335-46-7	C₁₉H₂₁NOS	详情	详情

Extended Information