6-bromo-2,2-dimethyl-2H-chromene -Drug Synthesis Database

【结构式】

【分子编号】34890

【品名】6-bromo-2,2-dimethyl-2H-chromene

【CA登记号】

【分子式】C₁₁H₁₁BrO

【分子量】239.11174

【元素组成】C 55.25% H 4.64% Br 33.42% O 6.69%

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：(V)

Treatment of 2-methyl-3-butyn-2-ol (I) with trifluoroacetic anhydride and DBU gave trifluoroacetate (II), which was condensed with 4-bromophenol (III) in the presence of CuCl2 to afford propargyl ether (IV). Cyclization of (IV) in N,N-diethylaniline at 185 C produced benzopyran (V). The required sulfonyl group was introduced in (V) by lithium-bromine exchange, followed by reaction with sulfur dioxide to give the lithium sulfinate (VI), and then oxidation to the sulfonyl chloride (VII) by means of sulfuryl chloride (1). Subsequent treatment of (VII) with diisobutylamine yielded sulfonamide (VIII). Asymmetric epoxidation of (VIII) using sodium hypochlorite and (S,S)(+)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino-manganese(III) chloride (Jacobsen's catalyst) gave rise to epoxide (IX), which was opened with ammonium hydroxide to furnish the trans aminoalcohol (X). Finally, coupling of (X) with N-chlorophenyl-N'-cyanothiourea (XI) in the presence of EDC provided the title cyanoguanidine derivative.

参考文献中间体

合成目标

【1】 Grover, G.J.; Ding, C.Z.; Miller, A.V.; Rovnyak, G.C.; Ahmed, S.Z.; Misra, R.N.; Normandin, D.E.; Atwal, K.S.; Kelly, Y.; Sleph, P.G.; Cardioselective antiischemic ATP-sensitive potassium channel (KATP) openers. 6. Effect of modifications at C6 of benzopyranyl cyanoguanidines. J Med Chem 1999, 42, 18, 3711.
【2】 Ding, C.Z.; Atwal, K.S. (Bristol-Myers Squibb Co.); Sulfonamido substd. benzopyran potassium channel activators. CA 2178353; EP 0747374; JP 1997003035; US 5869478 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	33862	trifluoroacetic anhydride	407-25-0	C₄F₆O₃	详情	详情
(I)	17922	2-methyl-3-butyn-2-ol; 3-Methyl butynol	115-19-5	C₅H₈O	详情	详情
(II)	34888	1,1-dimethyl-2-propynyl 2,2,2-trifluoroacetate		C₇H₇F₃O₂	详情	详情
(III)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(IV)	34889	1-bromo-4-[(1,1-dimethyl-2-propynyl)oxy]benzene; 4-bromophenyl 1,1-dimethyl-2-propynyl ether		C₁₁H₁₁BrO	详情	详情
(V)	34890	6-bromo-2,2-dimethyl-2H-chromene		C₁₁H₁₁BrO	详情	详情
(VI)	34891	lithium 2,2-dimethyl-2H-chromene-6-sulfinate		C₁₁H₁₁LiO₃S	详情	详情
(VII)	34892	2,2-dimethyl-2H-chromene-6-sulfonyl chloride		C₁₁H₁₁ClO₃S	详情	详情
(VIII)	34893	N,N-diisobutyl-2,2-dimethyl-2H-chromene-6-sulfonamide		C₁₉H₂₉NO₃S	详情	详情
(IX)	34894	(1aS,7bS)-N,N-diisobutyl-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-sulfonamide		C₁₉H₂₉NO₄S	详情	详情
(X)	34895	(3S,4R)-4-amino-3-hydroxy-N,N-diisobutyl-2,2-dimethyl-3,4-dihydro-2H-chromene-6-sulfonamide		C₁₉H₃₂N₂O₄S	详情	详情
(XI)	34896	N-(4-chlorophenyl)-N'-cyanothiourea		C₈H₆ClN₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Lithiation of 6-bromo-2,2-dimethyl-2H-1-benzopyran (I), followed by treatment with sulfur dioxide, gave the sulfinic acid (II), which was subsequently chlorinated to sulfonyl chloride (III) employing SO2Cl2. Condensation of sulfonyl chloride (III) with aniline furnished the target N-phenyl sulfonamide (IV).

参考文献中间体

合成目标

【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); Benzopyrans and pharmaceutical compsns. containing them. EP 0828733; JP 1999505820; US 5905156; WO 9637490 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	34890	6-bromo-2,2-dimethyl-2H-chromene	C₁₁H₁₁BrO	详情	详情
(II)	54657	2,2-dimethyl-2H-chromene-6-sulfinic acid	C₁₁H₁₂O₃S	详情	详情
(III)	34892	2,2-dimethyl-2H-chromene-6-sulfonyl chloride	C₁₁H₁₁ClO₃S	详情	详情
(IV)	54658	2,2-dimethyl-N-phenyl-2H-chromene-6-sulfonamide	C₁₇H₁₇NO₃S	详情	详情

Extended Information