2,6-Diisopropylphenol -Drug Synthesis Database

【结构式】

【分子编号】20249

【品名】2,6-Diisopropylphenol

【CA登记号】2078-54-8

【分子式】C₁₂H₁₈O

【分子量】178.27432

【元素组成】C 80.85% H 10.18% O 8.97%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(VIII)

1) The reaction of (V) with SOCl2 or (COCl)2 in DMF affords the expected acyl chloride (VI), which is finally condensed with 2,6-diisopropylphenyl sulfamate (VII) by means of triethylamine in hot toluene to obtain Avasimibe. 2) The sulfamate (VII) can be obtained by condensation of 2,6-diisopropylphenol (VIII) with chlorosulfonyl isocyanate (IX) in refluxing toluene to give the isocyanate (X), which is hydrolyzed with water to the sulfamate (VII). compound is condensed with the previously described isocyanate (X) in refluxing THF to obtain Avasimibe. 3) Avasimibe can also be obtained by condensation of isocyanate (X) with Grignard reagent (XIII).

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Rabasseda, X.; Castañer, J.; Avasimibe . Drugs Fut 1999, 24, 1, 9.
【2】 Lee, H.T.; Picad, J.A.; Sliskovic, D.R.; Wierenga, W. (Pfizer Inc.); N-Acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents. EP 0698010; JP 1996510256; US 5491172; WO 9426702 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	20240	2-(2,4,6-triisopropylphenyl)acetic acid		C₁₇H₂₆O₂	详情	详情
(VI)	20247	2-(2,4,6-triisopropylphenyl)acetyl chloride		C₁₇H₂₅ClO	详情	详情
(VII)	20248	2,6-diisopropylphenylsulfamate		C₁₂H₁₉NO₃S	详情	详情
(VIII)	20249	2,6-Diisopropylphenol	2078-54-8	C₁₂H₁₈O	详情	详情
(IX)	14101	Chlorosulfonyl isocyanate	1189-71-5	CClNO₃S	详情	详情
(X)	20251	2-[(isocyanatosulfonyl)oxy]-1,3-diisopropylbenzene		C₁₃H₁₇NO₄S	详情	详情
(XIII)	20243	bromo(2,4,6-triisopropylbenzyl)magnesium		C₁₆H₂₅BrMg	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The title compound was obtained by iodination of 2,6-diisopropylphenol (propofol) (I) employing either potassium iodide and hydrogen peroxide or iodonium chloride in HOAc.

参考文献中间体

合成目标

【1】 Altomare, C.; Latrofa, A.; Usala, M.; Sanna, E.; Liso, G.; Franco, M.; Biggio, G.; Trapani, G.; Propofol analogues. Synthesis, relationships between structure and affinity at GABAA receptor in rat brain, and differential electrophysiological profile at recombinant human GABAA receptors. J Med Chem 1998, 41, 11, 1846.
【2】 Bonal, J.; et al. (Bobel246 SL); Use derivatives of 2,4-bisubstituted phenols as 5-lipoxigenase inhibitors. WO 9521610 .

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)	20249	2,6-Diisopropylphenol	2078-54-8	C₁₂H₁₈O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The title compound was obtained by Mannich reaction between 2,6-diisopropylphenol (I), morpholine (II) and formaldehyde, followed by conversion to the corresponding hydrochloride salt.

参考文献中间体

合成目标

【1】 Cooke, A.; et al.; Water-soluble propofol analogues with intravenous anaesthetic activity. Bioorg Med Chem Lett 2001, 11, 7, 927.
【2】 Buchanan, K.; et al.; Novel water-soluble propofol analogs with intravenous anaesthetic activities. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 226.

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)	20249	2,6-Diisopropylphenol	2078-54-8	C₁₂H₁₈O	详情	详情
(II)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Methylation of 2,6-diisopropylphenol (I) with iodomethane and K2CO3 provides ether (II). Subsequent treatment with iodine and nitric acid gives rise to the diaryl iodonium compound (III), isolated as the corresponding tetrafluoroborate salt. 3,5-Dibromo-4-hydroxybenzoic acid (IV) is esterified with methanol and thionyl chloride to produce (V). Copper-promoted coupling between hydroxybenzoate (V) and the diaryl iodonium salt (III) leads to diaryl ether (VI). Finally, simultaneous cleavage of the methyl ether and ester groups of (VI) is achieved by means of boron tribromide in cold CH2Cl2

参考文献中间体

合成目标

【1】 Baxter, J.D.; Goede, P.; Apriletti, J.W.; et al.; Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology 2002, 143, 2, 517.
【2】 Baxter, J.D.; Scanlan, T.S.; Fletterick, R.J.; Wagner, R.L.; Kushner, P.J.; West, B.L.; Shiau, A.K.; Apriletti, J.W. (University of California, Oakland); Nuclear receptor ligands and ligand binding domains. CA 2314096; EP 1034184; US 6266622; WO 9926966 .
【3】 Brenneisen,P.; et al. (Ciba Geigy Corp.); Nuclear receptor ligands and ligand binding domains. DE 1932690; DE 1935338; US 3839582 .

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)	20249	2,6-Diisopropylphenol	2078-54-8	C₁₂H₁₈O	详情	详情
(II)	60874	2,6-diisopropylphenyl methyl ether; 1,3-diisopropyl-2-methoxybenzene		C₁₃H₂₀O	详情	详情
(III)	60875	bis(3,5-diisopropyl-4-methoxyphenyl)iodonium		C₂₆H₃₈IO₂	详情	详情
(IV)	10115	3,5-Dibromo-4-hydroxybenzoic acid	3337-62-0	C₇H₄Br₂O₃	详情	详情
(V)	10116	methyl 3,5-dibromo-4-hydroxybenzoate	41727-47-3	C₈H₆Br₂O₃	详情	详情
(VI)	60876	methyl 3,5-dibromo-4-(3,5-diisopropyl-4-methoxyphenoxy)benzoate		C₂₁H₂₄Br₂O₄	详情	详情

Extended Information