2-Amino-5-chlorobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】10285

【品名】2-Amino-5-chlorobenzoic acid

【CA登记号】635-21-2

【分子式】C₇H₆ClNO₂

【分子量】171.58288

【元素组成】C 49% H 3.52% Cl 20.66% N 8.16% O 18.65%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VIII)

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：(XI)

The starting benzophenone (I) can also be obtained in several different ways: a) By a Friedel-Crafts reaction of p-chloroaniline (X) and benzoyl chloride (D). b) By reaction of 5-chloroanthranilic acid (XI) with acetic anhydride to the bicyclic compound (XII), which is then submitted to a Grignard reaction with phenylmagnesium bromide (E). c) By oxidation of 2,3-diphenyl-5-chloroindole (XIII) with CrO3 to the N-benzoylbenzophenone (XIV), followed by debenzoylation with NaOH.

参考文献中间体

合成目标

【1】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .
【2】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(D)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(E)	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(I)	10279	(2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone	719-59-5	C₁₃H₁₀ClNO	详情	详情
(X)	12034	4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline	106-47-8	C₆H₆ClN	详情	详情
(XI)	10285	2-Amino-5-chlorobenzoic acid	635-21-2	C₇H₆ClNO₂	详情	详情
(XII)	33853	6-chloro-2-methyl-4H-3,1-benzoxazin-4-one		C₉H₆ClNO₂	详情	详情
(XIII)	33854	5-chloro-2,3-diphenyl-1H-indole		C₂₀H₁₄ClN	详情	详情
(XIV)	33855	N-(2-benzoyl-4-chlorophenyl)benzamide		C₂₀H₁₄ClNO₂	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 precursor 5-chloro-2-tetrazol-1-yl-benzylamine (V) is prepared as follows. Cyclization of 5-chloroanthranilic acid (I) with sodium azide and trimethyl orthoformate gives rise to the tetrazole derivative (II). Subsequent coupling of acid (II) with ammonium chloride in the presence of EDC and HOAt affords amide (III). This is then dehydrated to the nitrile (IV) employing the Burgess reagent in THF. Nitrile (IV) is reduced to the target amine (V) by catalytic hydrogenation over Raney nickel.

参考文献中间体

合成目标

【1】 Williams, P.D.; Selnick, H.G.; Young, M.B.; Nantermet, P.G. (Merck & Co., Inc.); Thrombin inhibitors. EP 1359913; WO 0264140 .

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)	10285	2-Amino-5-chlorobenzoic acid	635-21-2	C₇H₆ClNO₂	详情	详情
(II)	63209	5-chloro-2-(1H-1,2,3,4-tetraazol-1-yl)benzoic acid		C₈H₅ClN₄O₂	详情	详情
(III)	63210	5-chloro-2-(1H-1,2,3,4-tetraazol-1-yl)benzamide		C₈H₆ClN₅O	详情	详情
(IV)	63211	5-chloro-2-(1H-1,2,3,4-tetraazol-1-yl)benzonitrile		C₈H₄ClN₅	详情	详情
(V)	63212	[5-chloro-2-(1H-1,2,3,4-tetraazol-1-yl)phenyl]methanamine; 5-chloro-2-(1H-1,2,3,4-tetraazol-1-yl)benzylamine		C₈H₈ClN₅	详情	详情

Extended Information