6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine -Drug Synthesis Database

【结构式】

【分子编号】55631

【品名】6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine

【CA登记号】7499-66-3

【分子式】C₁₀H₈BrN

【分子量】222.08426

【元素组成】C 54.08% H 3.63% Br 35.98% N 6.31%

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：(II)

6-Bromo-2-naphthylamine (II) was prepared from the corresponding naphthol (I) by treatment with ammonium hydroxide. Coupling of amine (II) with 4-[(methoxycarbonyl)methoxy]benzoic acid (III) by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) provided amide (IV). This was converted to nitrile (V) by displacement of the bromide with CuCN in hot 1,3-dimethyl-2-imidazolinone. Addition of H2S to the cyano group of (V) produced thioamide (VI), which was further alkylated with iodomethane to yield the thioimidate (VII). Amidine (VIII) was then prepared by treatment of (VII) with ammonium acetate. Finally, selective hydrolysis of the methyl ester group of (VIII) by means of NaOH gave rise to the title compound.

参考文献中间体

合成目标

【1】 Yoshida, T.; Fukaya, C.; Inoue, Y.; Ashimori, A.; Kosaka, K.; Imada, T.; Nakamura, N.; Ono, S.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 1. The selection of naphthalene derivatives. Chem Pharm Bull 1999, 47, 12, 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)	44398	6-bromo-2-naphthol	15231-91-1	C₁₀H₇BrO	详情	详情
(II)	55631	6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine	7499-66-3	C₁₀H₈BrN	详情	详情
(III)	55632	4-(2-methoxy-2-oxoethoxy)benzoic acid		C₁₀H₁₀O₅	详情	详情
(IV)	55633	methyl 2-(4-{[(6-bromo-2-naphthyl)amino]carbonyl}phenoxy)acetate		C₂₀H₁₆BrNO₄	详情	详情
(V)	55634	methyl 2-(4-{[(6-cyano-2-naphthyl)amino]carbonyl}phenoxy)acetate		C₂₁H₁₆N₂O₄	详情	详情
(VI)	55635	methyl 2-[4-({[6-(aminocarbothioyl)-2-naphthyl]amino}carbonyl)phenoxy]acetate		C₂₁H₁₈N₂O₄S	详情	详情
(VII)	55636	2,6-Dihydroxybenzoic acid; gamma-Resorcylic acid; Resorcinol-2-carboxylic acid	303-07-1	C₂₂H₂₀N₂O₄S	详情	详情
(VIII)	55637	2,6-Dihydroxybenzoic acid methyl ester; gamma-Resorcylic acid methyl ester	2150-45-0	C₂₁H₁₉N₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

The boronate intermediate (XI) is prepared by hydrolysis of methyl 6-bromo-2-naphthoate (XII) with LiOH in H2O/THF to give 6-bromo-2-naphthoic acid (XIII), which by Curtius rearrangement with DPPA and Et3N in DMF at 100 °C yields 6-bromo-2-naphthylamine (XIv). Sulfonylation of amine (XIv) with mesyl chloride (Xv) in pyridine provides the sulfonamido naphthalene (XvI), which finally undergoes borylation with bis(pinacolato)diboron in the presence of KOAc and combiPhos-Pd6 catalyst in refluxing toluene .

参考文献中间体

合成目标

【1】 Pratt, J.K., Betebenner, D., Flentge, C. et al. Aryl 1-uracil inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase: Uracil ring replacements. 244th ACS Natl Meet (August 19-23, Philadelphia) 2012, Abst MEDI 146.
【2】 Wagner, R., Tufano, M.D., Stewart, K.D. et al. (Abbvie Bahamas Ltd.). Uracil or thymine derivative for treating hepatitis C. CN 101801935, CN 102746239, EP 2222646, JP 2010539186, US 2012213733, WO 2009039127.
【3】 Flentge, C.A., Hutchinson, D.K., Betebenner, D.A. et al. (Abbott Laboratories). Anti-infective pyrimidines and uses thereof. CN 101842360, CN 102746240, EP 2203431, EP 2368882, EP 2639226, JP 2010539187, US 8188104, US 2012244119, US 8501238, WO 2009039134.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	67686	N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)methanesulfonamide		C₁₇H₂₂BNO₄S	详情	详情
(XII)	59539	6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate	33626-98-1	C₁₂H₉BrO₂	详情	详情
(XIII)	42564	6-Bromo-2-naphthoic acid；(6-Bromonaphthalen-2-yl)acetic acid;6-Bromo-2-naphthalenecarboxylic acid	5773-80-8	C₁₁H₇BrO₂	详情	详情
(XIV)	55631	6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine	7499-66-3	C₁₀H₈BrN	详情	详情
(XV)	13467	Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride	124-63-0	CH₃ClO₂S	详情	详情
(XVI)	67687	N-(5-bromonaphthalen-1-yl)methanesulfonamide		C₁₁H₁₀BrNO₂S	详情	详情

Extended Information