benzyl 2-hydroxyethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】32497

【品名】benzyl 2-hydroxyethylcarbamate

【CA登记号】77987-49-6

【分子式】C₁₀H₁₃NO₃

【分子量】195.21816

【元素组成】C 61.53% H 6.71% N 7.17% O 24.59%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XI)

The acetylation of 5-bromopyridine-2-amine (I) with acetic anhydride in AcOH gives the expected amide (II), which is alkylated with ethylene by means of palladium acetate, tri p-tolylphosphine and triethylamine in hot acetonitrile to yield N-(5-vinylpyridin-2-yl)acetamide (III). The regioselective dihydroxylation of the vinyl group of (III) with AD-Mix-B in tert-butanol affords N-[5-(1(R),2-dihydroxyethyl)pyridin-2-yl]acetamide (IV), which is monotosylated with Ts-Cl in cool pyridine to give the tosylate (V). The reaction of (V) with potassium tert.-butoxide in THF yields the epoxide (VI), which is condensed with 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) in hot toluene/DMSO to provide the expected addition product (VIII). Finally, this compound is treated with 6N HCl on a steam bath. The intermediate 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) has been obtained as follows: The reaction of benzyl chloroformate (IX) with ethanolamine (X) by means of NaHCO3 in water gives the carbamate (XI), which is condensed with 2-(4-hydroxyphenyl)-N-methylacetamide (XII) (obtained by reaction of the corresponding methyl ester (XIII) with methylamine), by means of PPh3 and diisopropyl azodicarboxylate (DIAD) in THF yielding the intermediate (XIV). Finally, this compound is submitted to elimination of the carbamate protecting group by hydrogenation with H2 over Pd/C in methanol to provide the target intermediate (VII).

参考文献中间体

合成目标

【1】 Dow, R.L. (Pfizer Inc.); beta-Adrenergic agonists to reduce a wasting condition. EP 0887079 .
【2】 Devries, K.M.; Dow, R.L.; Wright, S.W. (Pfizer Inc.); Process for substd. pyridines. EP 0938476; WO 9821184 .

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)	32490	N-(5-bromo-2-pyridinyl)acetamide		C₇H₇BrN₂O	详情	详情
(III)	32491	N-(5-vinyl-2-pyridinyl)acetamide		C₉H₁₀N₂O	详情	详情
(IV)	32492	N-[5-[(1R)-1,2-dihydroxyethyl]-2-pyridinyl]acetamide		C₉H₁₂N₂O₃	详情	详情
(V)	32493	(2R)-2-[6-(acetamido)-3-pyridinyl]-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₆H₁₈N₂O₅S	详情	详情
(VI)	32494	N-[5-[(2R)oxiranyl]-2-pyridinyl]acetamide		C₉H₁₀N₂O₂	详情	详情
(VII)	32495	2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide		C₁₁H₁₆N₂O₂	详情	详情
(VIII)	32496	2-[4-[2-([(2R)-2-[6-(acetamido)-3-pyridinyl]-2-hydroxyethyl]amino)ethoxy]phenyl]-N-methylacetamide		C₂₀H₂₆N₄O₄	详情	详情
(IX)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(X)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(XI)	32497	benzyl 2-hydroxyethylcarbamate	77987-49-6	C₁₀H₁₃NO₃	详情	详情
(XII)	32498	2-(4-hydroxyphenyl)-N-methylacetamide		C₉H₁₁NO₂	详情	详情
(XIII)	15822	Methyl 4-hydroxyphenylacetate; methyl 2-(4-hydroxyphenyl)acetate	14199-15-6	C₉H₁₀O₃	详情	详情
(XIV)	32499	benzyl 2-[4-[2-(methylamino)-2-oxoethyl]phenoxy]ethylcarbamate		C₁₉H₂₂N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Ethanolamine (I) was protected as the N-benzyloxycarbonyl derivative (II) and subsequently converted to tosylate (III). Alkylation of N,N,N'-trimethylethylenediamine (IV) with tosylate (III) produced triamine (V). The benzyloxycarbonyl protecting group was then removed by transfer hydrogenolysis with ammonium formate and Pd/C to yield triamine (VI).

参考文献中间体

合成目标

【1】 Ritchie, T.J.; Hallett, A.; Dziadulewicz, E.K.; et al.; 1-(2-Nitrophenyl)thiosemicarbazides: A novel class of potent, orally active non-peptide antagonist for the bradykinin B2 receptor. J Med Chem 2000, 43, 5, 769.

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)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(II)	32497	benzyl 2-hydroxyethylcarbamate	77987-49-6	C₁₀H₁₃NO₃	详情	详情
(III)	42170	2-[[(benzyloxy)carbonyl]amino]ethyl 4-methylbenzenesulfonate		C₁₇H₁₉NO₅S	详情	详情
(IV)	15778	N-[2-(dimethylamino)ethyl]-N-methylamine; N,N,N'-trimethyl-1,2-ethanediamine; N(1),N(1),N(2)-trimethyl-1,2-ethanediamine	142-25-6	C₅H₁₄N₂	详情	详情
(V)	42316	benzyl 2-[[2-(dimethylamino)ethyl](methyl)amino]ethylcarbamate		C₁₅H₂₅N₃O₂	详情	详情
(VI)	42317	N-(2-aminoethyl)-N-[2-(dimethylamino)ethyl]-N-methylamine; N(1)-(2-aminoethyl)-N(1),N(2),N(2)-trimethyl-1,2-ethanediamine		C₇H₁₉N₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The precursor triamine (VI) is prepared as follows. Ethanolamine (I) is protected as the N-Cbz derivative (II) upon treatment with N-(benzyloxycarbonyloxy)succinimide. Subsequent tosylation of (II) to yield (III), followed by displacement of the tosylate of (III) with trimethyl propanediamine (IV) furnishes the protected triamine (V). Then, Cbz group hydrogenolysis in (V) in the presence of Pd/C gives rise to triamine (VI).

参考文献中间体

合成目标

【1】 Dziadulewicz, E.K.; et al.; Nonpeptide bradykinin B2 receptor antagonists: Conversion of rodent-selective bradyzide analogues into potent, orally-active human bradykinin B2 receptor antagonists. J Med Chem 2002, 45, 11, 2160.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	30663	N-benzyloxycarbonyloxysuccinimide; 1-[[(Benzyloxy)carbonyl]oxy]-2,5-pyrrolidinedione	13139-17-8	C₁₂H₁₁NO₅	详情	详情
(I)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(II)	32497	benzyl 2-hydroxyethylcarbamate	77987-49-6	C₁₀H₁₃NO₃	详情	详情
(III)	42170	2-[[(benzyloxy)carbonyl]amino]ethyl 4-methylbenzenesulfonate		C₁₇H₁₉NO₅S	详情	详情
(IV)	28165	N-[3-(dimethylamino)propyl]-N-methylamine	4543-96-8	C₆H₁₆N₂	详情	详情
(V)	61665	benzyl 2-[[3-(dimethylamino)propyl](methyl)amino]ethylcarbamate		C₁₆H₂₇N₃O₂	详情	详情
(VI)	61664	N~1~-(2-aminoethyl)-N~1~,N~3~,N~3~-trimethyl-1,3-propanediamine		C₈H₂₁N₃	详情	详情

Extended Information