methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate -Drug Synthesis Database

【结构式】

【分子编号】26465

【品名】methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate

【CA登记号】

【分子式】C₇H₁₂O₄

【分子量】160.16988

【元素组成】C 52.49% H 7.55% O 39.96%

与该中间体有关的原料药合成路线共 5 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5

合成路线1

该中间体在本合成路线中的序号：(III)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.

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)	12123	5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine	1072-97-5	C₅H₅BrN₂	详情	详情
(II)	11990	Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole	6160-65-2	C₇H₆N₄S	详情	详情
(III)	26465	methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate		C₇H₁₂O₄	详情	详情
(IV)	31334	2-chlorophenethylamine; 2-(2-chlorophenyl)-1-ethanamine	13078-80-3	C₈H₁₀ClN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-chlorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.

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)	12123	5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine	1072-97-5	C₅H₅BrN₂	详情	详情
(II)	11990	Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole	6160-65-2	C₇H₆N₄S	详情	详情
(III)	26465	methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate		C₇H₁₂O₄	详情	详情
(IV)	31335	3-chlorophenethylamine; 2-(3-chlorophenyl)-1-ethanamine	13078-79-0	C₈H₁₀ClN	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Taxane intermediates (XIII) and (XIV) were prepared by two related ways. Wittig condensation of cyclopropanecarboxaldehyde (I) with methoxycarbonylmethylenetriphenyl phosphorane (II) gave methyl trans-cyclopropylacrylate (III). This was oxidized with potassium ferricyanide in the presence of OsO4 and the chiral catalyst 1,4-bis(9-O-dihydroquinidyl)phthalazine to furnish (2S,3R)-diol (IV). After conversion of (IV) to tosylate (V), its cyclization by means of K2CO3 produced epoxide (VI). Subsequent epoxide opening with NaN3 gave azide (VII), which was hydrogenated in the presence of Pd/C and di tert-butyl dicarbonate to furnish carbamate (VIII). Treatment of (VIII) with isopropenyl methyl ether (IX) and pyridinium tosylate, followed by ester hydrolysis, produced oxazolidine (X). This was coupled to protected taxane (XI) by means of DCC and DMAP to provide ester (XII). Oxazolidine hydrolysis in (XII) with formic acid, followed by reprotection of the amine with Boc2O, furnished intermediate (XIII). Optionally, the trichloroethoxycarbonyl groups of (XIII) were removed upon treatment with Zn and AcOH to produce intermediate (XIV).

参考文献中间体

合成目标

【1】 Tsujihari, K.; Hashiyama, T.; Ohashi, M.; Nakanishi, N. (Tanabe Seiyaku Co., Ltd.); Baccatin derivs. and processes for preparing the same. CA 2162759; EP 0712854; JP 1997151181; US 5589502 .

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)	26463	cyclopropanecarbaldehyde	1489-69-6	C₄H₆O	详情	详情
(II)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(III)	26464	methyl (E)-3-cyclopropyl-2-propenoate		C₇H₁₀O₂	详情	详情
(IV)	26465	methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate		C₇H₁₂O₄	详情	详情
(V)	26466	methyl (2S,3R)-3-cyclopropyl-3-hydroxy-2-[[(4-methylphenyl)sulfonyl]oxy]propanoate		C₁₄H₁₈O₆S	详情	详情
(VI)	26467	methyl (2R,3R)-3-cyclopropyl-2-oxiranecarboxylate		C₇H₁₀O₃	详情	详情
(VII)	26468	methyl (2R,3S)-3-azido-3-cyclopropyl-2-hydroxypropanoate		C₇H₁₁N₃O₃	详情	详情
(VIII)	26469	methyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-cyclopropyl-2-hydroxypropanoate		C₁₂H₂₁NO₅	详情	详情
(IX)	26470	3-methoxy-1-butene		C₅H₁₀O	详情	详情
(X)	26471	(4S,5R)-3-(tert-butoxycarbonyl)-4-cyclopropyl-2,2-dimethyl-1,3-oxazolidine-5-carboxylic acid		C₁₄H₂₃NO₅	详情	详情
(XI)	23892	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₅H₃₈Cl₆O₁₄	详情	详情
(XII)	26472	methyl (9S,12S)-4-methoxy-12-[[(2S,5S,8S,11R)-5-(4-methoxybenzyl)-2,6,8,11,15,15-hexamethyl-4,7,10,13-tetraoxo-14-oxa-3,6,9,12-tetraazahexadec-1-anoyl](methyl)amino]-11-oxo-2-oxa-10-azatricyclo[12.2.2.1(3,7)]nonadeca-1(16),3(19),4,6,14,17-hexaene-9-carboxylate		C₄₉H₅₉Cl₆NO₁₈	详情	详情
(XIII)	26473	methyl (9S,12S)-4-methoxy-12-[[(2S,5S,8S,11R)-5-(4-methoxybenzyl)-2,6,8,11,15,15-hexamethyl-4,7,10,13-tetraoxo-14-oxa-3,6,9,12-tetraazahexadec-1-anoyl](methyl)amino]-11-oxo-2-oxa-10-azatricyclo[12.2.2.1(3,7)]nonadeca-1(16),3(19),4,6,14,17-hexaene-9-carboxylate		C₄₆H₅₅Cl₆NO₁₈	详情	详情
(XIV)	26474	methyl (9S,12S)-4-methoxy-12-[[(2S,5S,8S,11R)-5-(4-methoxybenzyl)-2,6,8,11,15,15-hexamethyl-4,7,10,13-tetraoxo-14-oxa-3,6,9,12-tetraazahexadec-1-anoyl](methyl)amino]-11-oxo-2-oxa-10-azatricyclo[12.2.2.1(3,7)]nonadeca-1(16),3(19),4,6,14,17-hexaene-9-carboxylate		C₄₀H₅₃NO₁₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 2-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.
【2】 Uckun, F.M. (Parker Hughes Institute); NNI for treatment of multi-drug resistant HIV. WO 0056736 .

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)	12123	5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine	1072-97-5	C₅H₅BrN₂	详情	详情
(II)	11990	Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole	6160-65-2	C₇H₆N₄S	详情	详情
(III)	26465	methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate		C₇H₁₂O₄	详情	详情
(IV)	31333	2-fluorophenethylamine; 2-(2-fluorophenyl)-1-ethanamine		C₈H₁₀FN	详情	详情

合成路线5

该中间体在本合成路线中的序号：(III)

2-Amino-5-bromopyridine (I) was condensed with 1,1-thiocarbonyldiimidazole (II) in acetonitrile to furnish the precursor thiocarbonyl derivative (III). Further reaction of (III) with 3-fluorophenethylamine (IV) in DMF at 100 C gave the target thiourea.

参考文献中间体

合成目标

【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998, 6, 10, 1789.

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)	12123	5-Bromo-2-pyridinylamine; 5-Bromo-2-pyridinamine; 2-Amino-5-bromopyridine	1072-97-5	C₅H₅BrN₂	详情	详情
(II)	11990	Di(1H-imidazol-1-yl)methanethione; 1,1'-Thiocarbonyldiimidazole	6160-65-2	C₇H₆N₄S	详情	详情
(III)	26465	methyl (2S,3R)-3-cyclopropyl-2,3-dihydroxypropanoate		C₇H₁₂O₄	详情	详情
(IV)	31336	3-fluorophenethylamine; 2-(3-fluorophenyl)-1-ethanamine		C₈H₁₀FN	详情	详情

Extended Information