tert-butyl 2-(1-methylhydrazino)acetate -Drug Synthesis Database

【结构式】

【分子编号】61909

【品名】tert-butyl 2-(1-methylhydrazino)acetate

【CA登记号】

【分子式】C₇H₁₆N₂O₂

【分子量】160.21632

【元素组成】C 52.48% H 10.07% N 17.48% O 19.97%

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：(XII)

The activation of N-Boc-L-aspartic acid 4-O-tert-butyl ester (I) with isopropyl chloroformate (II) in THF gives the mixed anhydride (III), which is reduced with NaBH4 to yield the hydroxyester (IV). The Swern oxidation of (IV) affords the aldehyde (V), which is condensed with the phosphonate (VI) by means of BuLi to provide the hexenedioic diester (VII). The stepwise reduction of (VII) first by means of H2 over Pd/C and then with NaBH4 gives rise to the omega-hydroxy hexanoate (VIII). This is treated first with MsCl and TEA and then with NaN3 to yield a diastereomeric mixture of azido hexanoates (IX) and (X). After separation, the desired isomer (X) is hydrolyzed with LiOH to afford the corresponding carboxylic acid (XI), which is condensed with 2-(1-methylhydrazino)acetic acid tert-butyl ester (XII) by means of HATU and DIEA to provide the corresponding hydrazide (XIII). The reduction of the azido group of (XIII) by means of H2 over Pd/C or with PPh3 in THF/water provides the corresponding amino derivative (XIV), which is finally hydrolyzed and N-deprotected by means of 4M HCl in dioxane to furnish the target fluorinated deoxynegamycin.

参考文献中间体

合成目标

【1】 Raju, B.; Anandan, S.K.; Gu, S.; et al.; Fluorinated deoxynegamycin analogs: Synthesis and antimicrobial properties. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1686.

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)	37623	(2S)-4-(tert-butoxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid		C₁₃H₂₃NO₆	详情	详情
(II)	26492	2-[(chlorocarbonyl)oxy]propane	108-23-6	C₄H₇ClO₂	详情	详情
(III)	61849			C₁₇H₂₉NO₈	详情	详情
(IV)	61901	tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoate		C₁₃H₂₅NO₅	详情	详情
(V)	61902	tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxobutanoate		C₁₃H₂₃NO₅	详情	详情
(VI)	61903	propyl 2-(dipropoxyphosphoryl)-2-fluoroacetate		C₁₁H₂₂FO₅P	详情	详情
(VII)	61904	6-(tert-butyl) 1-propyl (Z,4S)-4-[(tert-butoxycarbonyl)amino]-2-fluoro-2-hexenedioate		C₁₈H₃₀FNO₆	详情	详情
(VIII)	61905	tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-5-fluoro-6-hydroxyhexanoate		C₁₅H₂₈FNO₅	详情	详情
(IX)	61906	tert-butyl (3S,5S)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoate		C₁₅H₂₇FN₄O₄	详情	详情
(X)	61907	tert-butyl (3S,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoate		C₁₅H₂₇FN₄O₄	详情	详情
(XI)	61908	(3S,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoic acid		C₁₁H₁₉FN₄O₄	详情	详情
(XII)	61909	tert-butyl 2-(1-methylhydrazino)acetate		C₇H₁₆N₂O₂	详情	详情
(XIII)	61910	tert-butyl (7S)-7-[(2S)-3-azido-2-fluoropropyl]-3,11,11-trimethyl-5,9-dioxo-10-oxa-3,4,6,8-tetraazadodecan-1-oate		C₁₇H₃₂FN₇O₅	详情	详情
(XIV)	61911	tert-butyl (7R)-7-[(2R)-3-amino-2-fluoropropyl]-3,11,11-trimethyl-5,9-dioxo-10-oxa-3,4,6,8-tetraazadodecan-1-oate		C₁₇H₃₄FN₅O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of 3(R)-(tert-butoxycarbonylamino)-5-hexenoic acid (I) first with KI and I2, and then with NaN3 gives 6-azido-3(R)-(tert-butoxycarbonylamino)hexano-5-lactone (II), which is hydrolyzed with LiOH and protected with Tbdms-Cl to yield 6-azido-3(R)-(tert-butoxycarbonylamino)-5-(tert-butyldimethylsilyloxy)hexanoic acid (III). The reaction of acid (III) with pentafluorophenyl trifluoroacetate affords the corresponding activated ester as a mixture of diastereomers (IV) + (V). After separation, the desired diastereomer (IV) is condensed with 2-(1-methylhydrazino)acetic acid tert-butyl ester (VI) to provide the corresponding hydrazide (VII), which is reduced at the azido group by means of PPh3 in THF/water to give the amino compound (VIII). The condensation of (VIII) with 2-nitrophenylsulfonyl chloride (IX) by means of collidine in dichloromethane yields the sulfonamide (X), which is methylated with MeI and Cs2CO3 in DMF to afford the N-methylsulfonamide (XI). Finally, this compound is deprotected by reaction first with PhSH and K2CO3 and then with 4M HCl to provide the target hydrazide.

参考文献中间体

合成目标

【1】 Raju, B.; Mortell, K.; O'Dowd, H.; et al.; N- and C-terminal modifications of negamycin. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1685.

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)	61916	N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide		C₁₇H₁₈N₄O₃S	详情	详情
(II)	61923	tert-butyl (4R)-2-(azidomethyl)-6-oxotetrahydro-2H-pyran-4-ylcarbamate		C₁₁H₁₈N₄O₄	详情	详情
(III)	61924	(3R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoic acid		C₁₇H₃₄N₄O₅Si	详情	详情
(IV)	61926	2,3,4,5,6-pentafluorophenyl (3R,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoate		C₂₃H₃₃F₅N₄O₅Si	详情	详情
(V)	61925	2,3,4,5,6-pentafluorophenyl (3R,5S)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoate		C₂₃H₃₃F₅N₄O₅Si	详情	详情
(VI)	61909	tert-butyl 2-(1-methylhydrazino)acetate		C₇H₁₆N₂O₂	详情	详情
(VII)	61927	tert-butyl 2-[2-((3R,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoyl)-1-methylhydrazino]acetate		C₂₄H₄₈N₆O₆Si	详情	详情
(VIII)	61928	tert-butyl 2-[2-((3R,5R)-6-amino-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoyl)-1-methylhydrazino]acetate		C₂₄H₅₀N₄O₆Si	详情	详情
(IX)	32624	2-Nitrobenzenesulfonyl chloride	1694-92-4	C₆H₄ClNO₄S	详情	详情
(X)	61929	tert-butyl 2-[2-((3R,5R)-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(2-nitrophenyl)sulfonyl]amino}hexanoyl)-1-methylhydrazino]acetate		C₃₀H₅₃N₅O₁₀SSi	详情	详情
(XI)	61930	tert-butyl 2-[2-((3R,5R)-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}-6-{methyl[(2-nitrophenyl)sulfonyl]amino}hexanoyl)-1-methylhydrazino]acetate		C₃₁H₅₅N₅O₁₀SSi	详情	详情

Extended Information