2-Cyanoethyl N,N-diisopropylphosphoramidochloridite -Drug Synthesis Database

【结构式】

【分子编号】22791

【品名】2-Cyanoethyl N,N-diisopropylphosphoramidochloridite

【CA登记号】89992-70-1

【分子式】C₉H₁₈ClN₂OP

【分子量】236.681262

【元素组成】C 45.67% H 7.67% Cl 14.98% N 11.84% O 6.76% P 13.09%

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：(VII)

The amidation of L-serine methyl ester (I) with ethylenediamine (II) gives the amide (III), which is reduced with borane/THF to 2(R)-(hydroxymethyl)diethylenetriamine (IV). The reaction of (IV) with bromoacetic acid tert-butyl ester (V) by means of DIEA in DMF affords the penta tert-butyl acetate (VI), which is condensed with the chlorophosphoramidite (VII) by means of DIEA in dichloromethane giving the phosphoramidite intermediate (VIII). The condensation of (VIII) with 4,4-diphenylcyclohexanol (IX) (see scheme 23537901b) by means of tetrazole in acetonitile, with simultaneous oxidation with tert-butyl hydroperoxide yields the phosphate (X), which is selectively hydrolyzed at the 2-cyanoethyl ester group with ammonia in methanol affording the ammonium phosphate (XI). Finally, the hydrolysis of (XI) with HCl in ether/water eliminates the tert-butyl groups affording the desired chelating ligand (XII)

参考文献中间体

合成目标

【1】 Scott, D.M.; Sajiki, H.; McMurray, T.J.; Lauffer, R.B. (Epix Medical, Inc.); Diagnostic imaging contrast agents with extended blood retention. WO 9623526 .

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)	20915	methyl (2S)-2-amino-3-hydroxypropanoate	5680-80-8	C₄H₉NO₃	详情	详情
(II)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(III)	30315	(2S)-2-amino-N-(2-aminoethyl)-3-hydroxypropanamide		C₅H₁₃N₃O₂	详情	详情
(IV)	30316	(2R)-2-amino-3-[(2-aminoethyl)amino]-1-propanol		C₅H₁₅N₃O	详情	详情
(V)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(VI)	30317	3,6,9-Tris(tert-butoxycarbonylmethyl)-4(R)-(hydroxymethyl)-3,6,9-triazaundecanedioic acid di-tert-butyl ester		C₃₅H₆₅N₃O₁₁	详情	详情
(VII)	22791	2-Cyanoethyl N,N-diisopropylphosphoramidochloridite	89992-70-1	C₉H₁₈ClN₂OP	详情	详情
(VIII)	30318	3,6,9-Tris(tert-butoxycarbonylmethyl)-4(R)-[2-cyanoethoxy(diisopropylamino)phosphinyloxymethyl]-3,6,9-triazaundecanedioic acid di-tert-butyl ester		C₄₄H₈₂N₅O₁₂P	详情	详情
(IX)	30319	4,4-diphenylcyclohexanol		C₁₈H₂₀O	详情	详情
(X)	30320	3,6,9-Tris(tert-butoxycarbonylmethyl)-4(R)-[2-cyanoethoxy(4,4-diphenylcyclohexyloxy)phosphoryloxymethyl]-3,6,9-triazaundecanedioic acid di-tert-butyl ester		C₅₆H₈₇N₄O₁₄P	详情	详情
(XI)	30321	3,6,9-Tris(tert-butoxycarbonylmethyl)-4(R)-[4,4-diphenylcyclohexyloxy(hydroxy)phosphoryloxymethyl]-3,6,9-triazaundecanedioic acid di-tert-butyl ester ammonium salt		C₅₃H₈₇N₄O₁₄P	详情	详情
(XII)	30322	3,6,9-Tris(carboxymethyl)-4(R)-[4,4-diphenylcyclohexyloxy(hydroxy)phosphoryloxymethyl]-3,6,9-triazaundecanedioic acid		C₃₃H₄₄N₃O₁₄P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

5'-O-(3,4-dibenzyloxybenzyl)thymidine (I) was converted to the corresponding phosphoramidite (III) upon treatment with 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite (II) in the presence of diisopropylethylamine. This was applied to an automatic DNA synthesizer and coupled to the polymer support-linked pentadeoxyribonucleotide sequence GGGAG (IV). The resulting oligonucleotide was liberated from the solid support using aqueous ammonia, and then purified by reverse phase-HPLC in the presence of a triethylammonium acetate buffer to furnish the title compound as the triethylammonium salt.

参考文献中间体

合成目标

【1】 Furukawa, H.; Momota, K.; Hotoda, H.; Koizumi, M.; Kaneko, M. (Sankyo Co., Ltd.); Modified oligodeoxyribonucleotides, their preparat. EP 0611075; JP 1995053587; JP 1995087982; US 5674856; US 5807837 .

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)	22790	1-[(2R,4S,5R)-5-([[3,4-bis(benzyloxy)benzyl]oxy]methyl)-4-hydroxytetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione		C₃₁H₃₂N₂O₇	详情	详情
(II)	22791	2-Cyanoethyl N,N-diisopropylphosphoramidochloridite	89992-70-1	C₉H₁₈ClN₂OP	详情	详情
(III)	22792	5-O-(3,4-Dibenzyloxybenzyl)-3-O-[2-cyanoethoxy(diisopropylamino)phosphinyl]thymidine; 5-O-(3,4-Dibenzyloxybenzyl)-3-O-[2-cyanoethoxy(diisopropylamino)phosphinyl]thymidine		C₄₀H₄₉N₄O₈P	详情	详情

Extended Information