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【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

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.

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.

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