合成路线:It can be prepared in several different ways:1) The acylation of p-anisidine (I) with cyclopropanecarboxylic acid (II) by means of ethyl chloroformate and triethylamine gives N-cyclopropanecarbonyl-p-anisidine (III),which is reduced with LiAlH4 in THF yielding N-cyclopropylmethyl-p-anisidine (IV).The reaction of (IV) with sodium cyanate in acetic acid affords N-cyclopropylmethyl-N-(p-anisyl)urea (V),which is cyclized with benzaldehyde (A) by means of methanesulfonic acid in refluxing toluene giving 1-cyclopropylmethyl-4-phenyl-6-methoxy-3,4-dihydro-2(1H)-quinazolinone (VI) (1).Finally this product is dehydrogenated by oxidation with KMnO4 in dioxane - water (1),by treatment with Cl2 or Br2 with or without a base (2),or by treatment with sulfur in refluxing o-dichlorobenzene (3).
参考文献标题:
文献作者:Yamamoto,M.; et al.
参考来源:DE 2656156
合成路线:2) The alkylation of 2-amino-5-methoxybenzophenone (VII) with cyclopropylmethyl chloride (B) by means of NaH in THF gives 2-cyclopropylmethylamino-5-methoxybenzophenone (VIII),which by reaction with ethylchloroformate (C) at 100 C yields 2-(N-cyclopropylmethylethoxycarbonylamino)-5-methoxybenzophenone (IX).Finally this compound is cyclized with ammonium acetate and KOH in DMSO at 130 C (4).3) The oxidation of 1-cyclopropylmethyl-3-phenyl-5-methoxyindole-2-carboxylic acid (2-carboxylic acid ethyl ester,or 2-carbonitrile) (Xa-c) with CrO3 in acetic acid - water gives 2-(N-cyclopropylmethyloxalylamino)-5-methoxybenzophenone (or ethoxalylamino or cyanocarbonylamino) (XIa-c),which can be hydrolyzed to the free amine (VIII) with KOH in DMSO - water (5).4) The amine (VIII) can also be cyclized with potassium cyanate in hot acetic acid (5,6).5) The amine (VIII) can also by cyclized by reaction with oxalyl chloride,followed by a treatment with sodium azide in acetone - water (7).
参考文献标题:
文献作者:Yamamoto,M.; et al.
参考来源:AU 319919; DE 2159655; FR 2117301; GB 1353789; JP 7618423
合成路线:2) The alkylation of 2-amino-5-methoxybenzophenone (VII) with cyclopropylmethyl chloride (B) by means of NaH in THF gives 2-cyclopropylmethylamino-5-methoxybenzophenone (VIII),which by reaction with ethylchloroformate (C) at 100 C yields 2-(N-cyclopropylmethylethoxycarbonylamino)-5-methoxybenzophenone (IX).Finally this compound is cyclized with ammonium acetate and KOH in DMSO at 130 C (4).3) The oxidation of 1-cyclopropylmethyl-3-phenyl-5-methoxyindole-2-carboxylic acid (2-carboxylic acid ethyl ester,or 2-carbonitrile) (Xa-c) with CrO3 in acetic acid - water gives 2-(N-cyclopropylmethyloxalylamino)-5-methoxybenzophenone (or ethoxalylamino or cyanocarbonylamino) (XIa-c),which can be hydrolyzed to the free amine (VIII) with KOH in DMSO - water (5).4) The amine (VIII) can also be cyclized with potassium cyanate in hot acetic acid (5,6).5) The amine (VIII) can also by cyclized by reaction with oxalyl chloride,followed by a treatment with sodium azide in acetone - water (7).
参考文献标题:
文献作者:Inaba,S.; et al.
参考来源:DE 2037693; GB 1313789; JP 7227106; JP 7229516; JP 7229517; US 3712892; US 3767797
合成路线:2) The alkylation of 2-amino-5-methoxybenzophenone (VII) with cyclopropylmethyl chloride (B) by means of NaH in THF gives 2-cyclopropylmethylamino-5-methoxybenzophenone (VIII),which by reaction with ethylchloroformate (C) at 100 C yields 2-(N-cyclopropylmethylethoxycarbonylamino)-5-methoxybenzophenone (IX).Finally this compound is cyclized with ammonium acetate and KOH in DMSO at 130 C (4).3) The oxidation of 1-cyclopropylmethyl-3-phenyl-5-methoxyindole-2-carboxylic acid (2-carboxylic acid ethyl ester,or 2-carbonitrile) (Xa-c) with CrO3 in acetic acid - water gives 2-(N-cyclopropylmethyloxalylamino)-5-methoxybenzophenone (or ethoxalylamino or cyanocarbonylamino) (XIa-c),which can be hydrolyzed to the free amine (VIII) with KOH in DMSO - water (5).4) The amine (VIII) can also be cyclized with potassium cyanate in hot acetic acid (5,6).5) The amine (VIII) can also by cyclized by reaction with oxalyl chloride,followed by a treatment with sodium azide in acetone - water (7).
参考文献标题:
文献作者:Inaba,S.; et al.
参考来源:ZA 7005270
合成路线:2) The alkylation of 2-amino-5-methoxybenzophenone (VII) with cyclopropylmethyl chloride (B) by means of NaH in THF gives 2-cyclopropylmethylamino-5-methoxybenzophenone (VIII),which by reaction with ethylchloroformate (C) at 100 C yields 2-(N-cyclopropylmethylethoxycarbonylamino)-5-methoxybenzophenone (IX).Finally this compound is cyclized with ammonium acetate and KOH in DMSO at 130 C (4).3) The oxidation of 1-cyclopropylmethyl-3-phenyl-5-methoxyindole-2-carboxylic acid (2-carboxylic acid ethyl ester,or 2-carbonitrile) (Xa-c) with CrO3 in acetic acid - water gives 2-(N-cyclopropylmethyloxalylamino)-5-methoxybenzophenone (or ethoxalylamino or cyanocarbonylamino) (XIa-c),which can be hydrolyzed to the free amine (VIII) with KOH in DMSO - water (5).4) The amine (VIII) can also be cyclized with potassium cyanate in hot acetic acid (5,6).5) The amine (VIII) can also by cyclized by reaction with oxalyl chloride,followed by a treatment with sodium azide in acetone - water (7).
参考文献标题:
文献作者:Ishizumi,K.; et al.
参考来源:AU 330189; CA 949575; GB 1398448; JP 7445085; NL 7312257; US 3926993
合成路线:It can be prepared in several different ways:1) The acylation of p-anisidine (I) with cyclopropanecarboxylic acid (II) by means of ethyl chloroformate and triethylamine gives N-cyclopropanecarbonyl-p-anisidine (III),which is reduced with LiAlH4 in THF yielding N-cyclopropylmethyl-p-anisidine (IV).The reaction of (IV) with sodium cyanate in acetic acid affords N-cyclopropylmethyl-N-(p-anisyl)urea (V),which is cyclized with benzaldehyde (A) by means of methanesulfonic acid in refluxing toluene giving 1-cyclopropylmethyl-4-phenyl-6-methoxy-3,4-dihydro-2(1H)-quinazolinone (VI) (1).Finally this product is dehydrogenated by oxidation with KMnO4 in dioxane - water (1),by treatment with Cl2 or Br2 with or without a base (2),or by treatment with sulfur in refluxing o-dichlorobenzene (3).
参考文献标题:Novel quinazoline derivatives.I.Synthesis and preliminary pharmacological evaluation of a antiinflamatory agent SL-573
文献作者:Komatsu,T.; et al.
参考来源:Arzneim-Forsch 1972,22(11),1958-1962
产品链接: CAS No. 33453-23-5››