Methyl triflate → O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(1-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate

HRID 1707450노트

반응식

HRID 1707450 반응식
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]=[N:68][NH:69][CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:71](N(C(C)C)CC)(C)C.[CH3:80]OS(C(F)(F)F)(=O)=O>ClCCl.O1CCCC1>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:60])([CH3:61])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]([CH3:71])[N:68]=[N:69][CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:60])([CH3:61])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]=[N:68][N:69]([CH3:80])[CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

참가 물질

7

반응물 3

HCID 9526Methyl triflateHCID 81531DiisopropylethylamineHCID 178452987HCID 178452987, 화합물

생성물 2

HCID 141566154O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(3-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate수율 30%HCID 141566156O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(1-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate수율 46%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (6.00 g: 5.87 mMol.) in a mixture of dichloromethane (60 ml) and tetrahydrofuran (30 ml) is added at -50° C. diisopropylethylamine (1.12 g: 6.43 mMol.). After stirring at -40°--50° C. for 3 minutes, trifluoromethanesulfonic acid methyl ester (0.73 ml: 6.45 mMol.) is added to the mixture. After stirring at the same temperature for 30 minutes, the reaction mixture is quenched with 10% hydrochloric acid (2.4 ml), diluted with water, and extracted with ethyl acetate. The extract is washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene: ethyl acetate=3:2) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(3-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester [1.84 g: Yield: 30%. NMR δ(CDCl3 -CD3OD) ppm: 1.52(s, 9H), 3.43, 3.55(ABq, J=17.3 Hz, 2H), 3.87, 3.94(ABq, J=13.7 Hz, 2H), 3.95(s, 3H), 5.12 (d, J=4.8 Hz, 1H), 5.99 (d, J=4.8 Hz, 1H), 6.96 (s, 1H), 7.06(s, 1H), 7.15-7.50(m, 25H), 7.73(s, 1H). IR ν(CHCl3) cm-1: 3398, 3300, 1784, 1714, 1683, 1540, 1490, 1443, 1366, 1277, 1220, 1153, 1114, 1077, 970, 910.], 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (2.71 g: Yield: 46%), and 7β-[(Z)-2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-trityloxyiminoacetamido]-3-(2-methyl-1,2,3-triazol-4-yl)-thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (0.51 g: Yield: 8%).

후처리

  1. stirringAfter stirring at the same temperature for 30 minutes
  2. customthe reaction mixture is quenched with 10% hydrochloric acid (2.4 ml)
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe extract is washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=3:2)

출처 및 근거

ORD 기록
ord-ee7c03e232dc4871a9c4adcb20725e55
출처 데이터셋
uspto-grants-1994_10
특허 번호
US05352792

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