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Dicyclohexylcarbodiimide → benzhydryl (6R,7R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1252316
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HRID 1252316 반응식
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27](O)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:38][C@@H:39]1[C:70](=[O:71])[N:41]2[C:42]([C:54]([O:56][CH:57]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)=[O:55])=[C:43]([CH2:46][S:47][C:48]3[N:52]([CH3:53])[N:51]=[N:50][N:49]=3)[CH2:44][S:45][C@H:40]12.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27]([NH:38][C@@H:39]2[C:70](=[O:71])[N:41]3[C:42]([C:54]([O:56][CH:57]([C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)[C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)=[O:55])=[C:43]([CH2:46][S:47][C:48]4[N:52]([CH3:53])[N:51]=[N:50][N:49]=4)[CH2:44][S:45][C@H:40]23)=[O:28])[N:25]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
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참가 물질

6

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 12873516(6R,7R)-Benzhydryl 7-amino-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 13335553(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid

생성물 1

HCID 141554879
benzhydryl (6R,7R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
수율 59%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

3.25 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid are dissolved in 200 ml of tetrahydrofuran, and 3.14 g of benzhydryl 7β-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate, 1.03 g of 1-hydroxybenzotriazole and 1.57 g of dicyclohexylcarbodiimide are added thereto. The mixture is stirred at room temperature for 2 hours. Insoluble materials are filtered off, and the filtrate is concentrated to dryness under reduced pressure. The residue is dissolved in ethyl acetate, and washed with 1% hydrochloric acid, 5% aqueous sodium bicarbonate solution and an aqueous saturated sodium chloride solution, successively. The ethyl acetate solution is then dried and concentrated to dryness under reduced pressure. The residue thus obtained is purified by silica gel chromatography (solvent, ethyl acetate: benzene=5:2). 3.7 g of benzhydryl 7β-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] -3-cephem-4-carboxylate are obtained.

후처리

  1. filtrationInsoluble materials are filtered off
  2. concentrationthe filtrate is concentrated to dryness under reduced pressure
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. washwashed with 1% hydrochloric acid, 5% aqueous sodium bicarbonate solution
  5. dry with materialThe ethyl acetate solution is then dried
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue thus obtained
  8. customis purified by silica gel chromatography (solvent, ethyl acetate: benzene=5:2)

출처 및 근거

ORD 기록
ord-e68e05c9efd249e0b97757cb5c742bd6
출처 데이터셋
uspto-grants-1988_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04742174

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