7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro -Drug Synthesis Database

【结构式】

【分子编号】10281

【品名】7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro

【CA登记号】1088-11-5

【分子式】C₁₅H₁₁ClN₂O

【分子量】270.71792

【元素组成】C 66.55% H 4.1% Cl 13.1% N 10.35% O 5.91%

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：(IV)

A new synthesis of adinazolam has been described: The condensation of phthaloyl-glycyl chloride (I) with 2-amino-5-chlorobenzophenone (II) in refluxing toluene gives 4-chloro-2-(phthaloylglycylamido)benzophenone (III), which is cyclized by means of hydrazine in refluxing ethanol yielding 7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one (IV). The reaction of (IV) with P2S5 in hot pyridine affords the corresponding thione (V), which is finally cyclized with N,N-dimethylglycine hydrazide by means of triethylamine in refluxing butanol. The starting products (I) and (II) are obtained as follows: The reaction of N-(ethoxycarbonyl)phthalimide (VI) with glycine by means of Na2CO3 in water gives the N-phthaloylglycine (VII), which is then treated with refluxing SOCl2 to give (I). The protection of 2-amino-4-chlorobenzoic acid (VIII) with tosyl chloride gives the corresponding N-tosyl derivative (IX), which by reaction with refluxing SOCl2 is converted into the acyl chloride (X). Finally, this compound is submitted to a Friedel-Craft's condensation with benzene and AlCl3 to afford (II).

参考文献中间体

合成目标

【1】 Johnson, T.D.; Hsi, R.S.P.; Carbon-14 labeled 1,4-benzodiazepines. 3. J Label Compd Radiopharm 1976, 12, 4, 613-619.
【2】 Castaner, J.; Pento, J.T.; Blancafort, P.; Serradell, M.N.; Adinazolam. Drugs Fut 1983, 8, 2, 87.
【3】 Stelzer, L.S.; Hsi, R.S.P.; Synthesis of adinazolam mesylate-multiply labeled with carbon-13 and deuterium. J Label Compd Radiopharm 1989, 26, 3, 287.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13364	Benzene	71-43-2	C₆H₆	详情	详情
	40924	2-(dimethylamino)acetohydrazide	539-64-0	C₄H₁₁N₃O	详情	详情
(I)	10278	2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride	6780-38-7	C₁₀H₆ClNO₃	详情	详情
(II)	10279	(2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone	719-59-5	C₁₃H₁₀ClNO	详情	详情
(III)	10280	N-(2-Benzoyl-4-chlorophenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide		C₂₃H₁₅ClN₂O₄	详情	详情
(IV)	10281	7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro	1088-11-5	C₁₅H₁₁ClN₂O	详情	详情
(V)	10282	7-Chloro-5-phenyl-3H-1,4-benzodiazepin-2-ylhydrosulfide; 7-Chloro-5-phenyl-3H-1,4-benzodiazepine-2-thiol		C₁₅H₁₁ClN₂S	详情	详情
(VI)	10283	ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide	22509-74-6	C₁₁H₉NO₄	详情	详情
(VII)	10284	N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid	4702-13-0	C₁₀H₇NO₄	详情	详情
(VIII)	10285	2-Amino-5-chlorobenzoic acid	635-21-2	C₇H₆ClNO₂	详情	详情
(IX)	10286	5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoic acid		C₁₄H₁₂ClNO₄S	详情	详情
(X)	10287	5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoyl chloride		C₁₄H₁₁Cl₂NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

1) The alkylation of 2-amino-5-chlorobenzophenone (I) with 2,2,2-trifluoroethyl trichloromethansulfonate (II) in refluxing xylene gives the N-trifluoroethyl derivative (III), which is then cyclized with glycine ethyl ester (A) in refluxing pyridine. 2) Compound (III) can also be bromoacetylated with bromoacetyl bromide (B) in refluxing benzene yielding the N-bromoacetyl compound (IV), which is then cyclized with ammonia in CHCl3. 3) By alkylation of 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (IX) with NaOMe and 2,2,2-trifluoroethyl iodide in MeOH.

参考文献中间体

合成目标

【1】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .
【2】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .
【3】 Topliss, J.G.; Verfahren zur Herstellung von neuen 1,4-benzodiazepinen bzw. ihren 4-Oxyden. CH 505842; DE 1793682; FR 1518382; GB 1179125 .
【4】 Castaner, J.; Thorpe, P.; Halazepam. Drugs Fut 1978, 3, 2, 109.
【5】 Topliss, J.G.; Steinman, M.; Alekel, R.; Wong, Y.S.; York, E.E.; 1-Polyfluoroalkylbenzodiazepines. J Med Chem 1973, 16, 12, 1354-60.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	18806	1,1,1-trifluoro-2-iodoethane	353-83-3	C₂H₂F₃I	详情	详情
(A)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(B)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(I)	10279	(2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone	719-59-5	C₁₃H₁₀ClNO	详情	详情
(II)	33474	2,2,2-Trifluoroethyl trichloromethanesulfonate; 2,2,2-Trifluoroethyl trichloromethylsulfonate	23199-56-6	C₃H₂Cl₃F₃O₃S	详情	详情
(III)	33848	[5-chloro-2-[(2,2,2-trifluoroethyl)amino]phenyl](phenyl)methanone		C₁₅H₁₁ClF₃NO	详情	详情
(IV)	33849	N-(2-benzoyl-4-chlorophenyl)-2-bromo-N-(2,2,2-trifluoroethyl)acetamide		C₁₇H₁₂BrClF₃NO₂	详情	详情
(IX)	10281	7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro	1088-11-5	C₁₅H₁₁ClN₂O	详情	详情

Extended Information