6-nitro-2,3-dihydro-4H-chromen-4-one -Drug Synthesis Database

【结构式】

【分子编号】23176

【品名】6-nitro-2,3-dihydro-4H-chromen-4-one

【CA登记号】

【分子式】C₉H₇NO₄

【分子量】193.15892

【元素组成】C 55.96% H 3.65% N 7.25% O 33.13%

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：(II)

Nitration of chromanone (I) with fuming HNO3 at -35 C afforded 6-nitro-4-chromanone (II). Subsequent aldol condensation of (II) with glyoxylic acid (III) in the presence of H2SO4 produced the alpha-beta-unsaturated acid (IV). Further hydrogenation of the nitro, keto, and olefin groups of (IV) with concomitant esterification produced the benzopyranylacetate (V). After protection of (V) as the N-Boc derivative (VI), optical resolution was achieved by preparative HPLC on a Chiralcel-OD column. The desired (S)-enantiomer (VI) was deprotected using ethanolic HCl to afford amine (VII), which was condensed with 4-cyanobenzoyl chloride (VIII) to give amide (IX). Treatment of (IX) with HCl-EtOH produced imidate (X), and subsequent treatment with morpholine (XI) furnished the target amidine, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Okumura, K.; Shimazaki, T.; Aoki, Y.; Yamashita, H.; Tanaka, E.; Banba, S.; Yazawa, K.; Kibayashi, K.; Banno, H.; New platelet fibrinogen receptor glycoprotein IIb-. J Med Chem 1998, 41, 21, 4036.

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)	14461	2,3-Dihydro-4H-chromen-4-one; 4-Chromanone	491-37-2	C₉H₈O₂	详情	详情
(II)	23176	6-nitro-2,3-dihydro-4H-chromen-4-one		C₉H₇NO₄	详情	详情
(III)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(IV)	23178	2-[6-nitro-4-oxo-2H-chromen-3(4H)-ylidene]acetic acid		C₁₁H₇NO₆	详情	详情
(V)	23179	methyl 2-(6-amino-3,4-dihydro-2H-chromen-3-yl)acetate		C₁₂H₁₅NO₃	详情	详情
(VI)	23180	methyl 2-[(3S)-6-[(tert-butoxycarbonyl)amino]-3,4-dihydro-2H-chromen-3-yl]acetate		C₁₇H₂₃NO₅	详情	详情
(VII)	23181	ethyl 2-[(3S)-6-amino-3,4-dihydro-2H-chromen-3-yl]acetate		C₁₃H₁₇NO₃	详情	详情
(VIII)	19280	4-cyanobenzoyl chloride	6068-72-0	C₈H₄ClNO	详情	详情
(IX)	23183	ethyl 2-[(3S)-6-[(4-cyanobenzoyl)amino]-3,4-dihydro-2H-chromen-3-yl]acetate		C₂₁H₂₀N₂O₄	详情	详情
(X)	23184	ethyl 2-[(3S)-6-([4-[ethoxy(imino)methyl]benzoyl]amino)-3,4-dihydro-2H-chromen-3-yl]acetate		C₂₃H₂₆N₂O₅	详情	详情
(XI)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Nitration of chromanone (I) with fuming HNO3 at -35 C afforded 6-nitro-4-chromanone (II). Subsequent aldol condensation of (II) with glyoxylic acid (III) in the presence of H2SO4 produced the alpha-beta-unsaturated acid (IV). Further hydrogenation of the nitro, keto, and olefin groups of (IV) with concomitant esterification produced the benzopyranylacetate (V). After protection of (V) as the N-Boc derivative (VI), optical resolution was achieved by preparative HPLC on a Chiralcel-OD column. The desired (S)-enantiomer (VI) was deprotected using ethanolic HCl to afford amine (VII), which was condensed with 4-cyanobenzoyl chloride (VIII) to give amide (IX). Treatment of (IX) with HCl-EtOH produced imidate (X), and subsequent treatment with morpholine (XI) furnished amidine (XII). Finally, basic hydrolysis of the ester function provided the target amidinoacid, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Okumura, K.; Shimazaki, T.; Aoki, Y.; Yamashita, H.; Tanaka, E.; Banba, S.; Yazawa, K.; Kibayashi, K.; Banno, H.; New platelet fibrinogen receptor glycoprotein IIb-. J Med Chem 1998, 41, 21, 4036.

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)	14461	2,3-Dihydro-4H-chromen-4-one; 4-Chromanone	491-37-2	C₉H₈O₂	详情	详情
(II)	23176	6-nitro-2,3-dihydro-4H-chromen-4-one		C₉H₇NO₄	详情	详情
(III)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(IV)	23178	2-[6-nitro-4-oxo-2H-chromen-3(4H)-ylidene]acetic acid		C₁₁H₇NO₆	详情	详情
(V)	23179	methyl 2-(6-amino-3,4-dihydro-2H-chromen-3-yl)acetate		C₁₂H₁₅NO₃	详情	详情
(VI)	23180	methyl 2-[(3S)-6-[(tert-butoxycarbonyl)amino]-3,4-dihydro-2H-chromen-3-yl]acetate		C₁₇H₂₃NO₅	详情	详情
(VII)	23181	ethyl 2-[(3S)-6-amino-3,4-dihydro-2H-chromen-3-yl]acetate		C₁₃H₁₇NO₃	详情	详情
(VIII)	19280	4-cyanobenzoyl chloride	6068-72-0	C₈H₄ClNO	详情	详情
(IX)	23183	ethyl 2-[(3S)-6-[(4-cyanobenzoyl)amino]-3,4-dihydro-2H-chromen-3-yl]acetate		C₂₁H₂₀N₂O₄	详情	详情
(X)	23184	ethyl 2-[(3S)-6-([4-[ethoxy(imino)methyl]benzoyl]amino)-3,4-dihydro-2H-chromen-3-yl]acetate		C₂₃H₂₆N₂O₅	详情	详情
(XI)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(XII)	23186	ethyl 2-[(3S)-6-([4-[imino(4-morpholinyl)methyl]benzoyl]amino)-3,4-dihydro-2H-chromen-3-yl]acetate		C₂₅H₂₉N₃O₅	详情	详情

Extended Information