2-amino-5-bromobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】31634

【品名】2-amino-5-bromobenzoic acid

【CA登记号】5794-88-7

【分子式】C₇H₆BrNO₂

【分子量】216.03418

【元素组成】C 38.92% H 2.8% Br 36.99% N 6.48% O 14.81%

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：(I)

The cyclization of 2-amino-5-bromobenzoic acid (I) with 3-phenylpropionyl chloride (II) by means of DMAP and Et3N in DMF gives the benzoxazinone (III), which by heating with glycine methyl ester (IV) yields the quinazolinone (V). The hydrolysis if (V) with NaOH in THF/water affords 2-[6-bromo-4-oxo-2-(2-phenylethyl)-3,4-dihydroquinazolin-3-yl]acetic acid (VI), which is condensed with the monoprotected hexane-1,6-diamine (VII), by means of HOBt, EDC and NMM to provide the amide (VIII). The condensation of (VIII) with phenylboronic acid (IX) by means of palladium tetrakis(triphenylphosphoine) gives the 6-phenyl substituted quinazolinone (X), which is finally deprotected with HCl.

参考文献中间体

合成目标

【1】 Ye, Z.; Bakshi, R.K.; Gao, Y.; et al.; Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues. Bioorg Med Chem Lett 2000, 10, 1, 5.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	16593	Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide	98-80-6	C₆H₇BO₂	详情	详情
(I)	31634	2-amino-5-bromobenzoic acid	5794-88-7	C₇H₆BrNO₂	详情	详情
(II)	16240	3-phenylpropanoyl chloride; Hydrocinnamoylchloride	645-45-4	C₉H₉ClO	详情	详情
(III)	31635	6-bromo-2-phenethyl-4H-3,1-benzoxazin-4-one		C₁₆H₁₂BrNO₂	详情	详情
(IV)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(V)	31636	methyl 2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetate		C₁₉H₁₇BrN₂O₃	详情	详情
(VI)	31637	2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetic acid		C₁₈H₁₅BrN₂O₃	详情	详情
(VII)	31638	tert-butyl 6-aminohexylcarbamate	51857-17-1	C₁₁H₂₄N₂O₂	详情	详情
(VIII)	31639	tert-butyl 6-([2-[6-bromo-4-oxo-2-phenethyl-3(4H)-quinazolinyl]acetyl]amino)hexylcarbamate		C₂₉H₃₇BrN₄O₄	详情	详情
(IX)	31640	tert-butyl 6-([2-[4-oxo-2-phenethyl-6-phenyl-3(4H)-quinazolinyl]acetyl]amino)hexylcarbamate		C₃₅H₄₂N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 5-bromoanthranilic acid (I) with the lithium derivative of 2-bromopyridine (II) in cold THF/ethyl ether gives the diaryl ketone (III). N-Fmoc-L-glutamic acid 5-methyl ester (IV) is chlorinated with oxalyl chloride and catalytic DMF to produce the acid chloride (V), which is then coupled with the amino ketone (III) in boiling chloroform to afford amide (VI). Base-mediated deprotection of amine (VI), followed by cyclization by treatment with AcOH in dichloroethane leads to the benzodiazepinone (VII). Subsequent treatment of lactam (VII) with bis-morpholinophosphorochloridate and NaH affords the imino phosphate (VIII), which is then condensed with 1-amino-2-propanol (IX) producing amidine (X). Finally, remimazolam is obtained by Swern oxidation of the secondary alcohol of (X), followed by cyclization under acidic conditions .

参考文献中间体

合成目标

【1】 Jung, D.K., Pacofsky, G.J., Stafford, J.A., Feldman, P.L., Kaldor, I., Tidwell, J.H. (GlaxoSmithKline plc). Short-acting benzodiazepines. EP 1183243, JP 2002544266, JP 2006151984, JP 2007197468, JP 2007197469, US 7160880, US 2007093475,US 2007135419, US 2007135420, US 2007135421, US 7435730, US 7528127, US 7473689, US 7485635, WO 2000069836

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)	31634	2-amino-5-bromobenzoic acid	5794-88-7	C₇H₆BrNO₂	详情	详情
(II)	29052	2-Bromopyridine；α-bromopyridine;α-bromoazine	109-04-6	C₅H₄BrN	详情	详情
(III)	68085	(2-amino-5-bromophenyl)(pyridin-2-yl)methanone	1563-56-0	C₁₂H₉BrN₂O	详情	详情
(IV)	68086	(R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-methoxy-5-oxopentanoic acidN-Fmoc-L-glutamic acid 5-methyl ester		C₂₁H₂₁NO₆	详情	详情
(V)	68087	(R)-methyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-chloro-5-oxopentanoate		C₂₁H₂₀ClNO₅	详情	详情
(VI)	68088	(S)-methyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-((4-bromo-2-picolinoylphenyl)amino)-5-oxopentanoate		C₃₃H₂₈BrN₃O₆	详情	详情
(VII)	68089	(S)-methyl 3-(7-bromo-2-oxo-5-(pyridin-2-yl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanoate		C₁₈H₁₆BrN₃O₃	详情	详情
(VIII)	68090	(S)-methyl 3-(7-bromo-2-((dimorpholinophosphoryl)oxy)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepin-3-yl)propanoate		C₂₆H₃₁BrN₅O₆P	详情	详情
(IX)	41397	1-amino-2-propanol	78-96-6	C₃H₉NO	详情	详情
(X)	68091	methyl 3-((3S)-7-bromo-2-((2-hydroxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepin-3-yl)propanoate		C₂₁H₂₃BrN₄O₃	详情	详情

Extended Information