Pyridine → benzhydryl (6R,7R)-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467370노트

반응식

HRID 467370 반응식
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][C:32]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)/[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.[Na+].CS(Cl)(=O)=O.[NH2:57][C@@H:58]1[C:89](=[O:90])[N:60]2[C:61]([C:73]([O:75][CH:76]([C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=3)[C:77]3[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=3)=[O:74])=[C:62]([CH2:65][S:66][C:67]3[CH2:71][O:70][C:69](=[O:72])[CH:68]=3)[CH2:63][S:64][C@H:59]12.N1C=CC=CC=1>CN(C)C=O>[O:72]=[C:69]1[CH:68]=[C:67]([S:66][CH2:65][C:62]2[CH2:63][S:64][C@@H:59]3[C@H:58]([NH:57][C:27](=[O:28])/[C:26](/[C:24]4[N:25]=[C:21]([NH:20][C:1]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)([C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[S:22][CH:23]=4)=[N:30]\[O:31][C:32]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:89](=[O:90])[N:60]3[C:61]=2[C:73]([O:75][CH:76]([C:83]2[CH:84]=[CH:85][CH:86]=[CH:87][CH:88]=2)[C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)=[O:74])[CH2:71][O:70]1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 23714200sodium (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetateHCID 67908483Diphenylmethyl 7beta-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate

생성물 1

HCID 141558982benzhydryl (6R,7R)-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate수율 64.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

A stirred solution of sodium 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetate (762 mg) in dimethylformamide (4 ml) was cooled to -55° C. to -60° C. and methanesulphonyl chloride (0.085 ml) was added. The mixture was stirred at the same temperature for 30 mins and then a solution of diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate (494 mg) in dimethylformamide (4 ml) was added followed by pyridine (0.08 ml). The mixture was then stirred at 0° C. for 90 mins and then partitioned between ethyl acetate and aqueous citric acid solution. The organic phase was washed successively with water, sodium bicarbonate solution, water, and brine. The solution was dried over magnesium sulphate and evaporated. The title compound (744 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel 2:1 going to 1:1 hexane:ethyl acetate). υmax (CHCl3) 3400, 1785, 1745 and 1685cm-1 . δH(CDCl3) 3.23 (1H, d, J 18.2Hz), 3.52 (1H, d, J 18.2Hz), 3.93 (1H, d, J 12.6Hz), 3.99 (1H, d, J 12.5Hz), 4.70 (2H, s), 5.08 (1H, d, J 5.0Hz),5.65 (1H, s), 6.11 (1H, dd, J 5.0 and 8.9Hz), 6.43 (1H, s), 6.75 (1H, s), 6.98 (1H, s), 7.15-7.5 (41H, m). [mass spectrum: +ve ion (thioglycerol) MH+ 1148].

후처리

  1. stirringThe mixture was then stirred at 0° C. for 90 mins
  2. custompartitioned between ethyl acetate and aqueous citric acid solution
  3. washThe organic phase was washed successively with water, sodium bicarbonate solution, water, and brine
  4. dry with materialThe solution was dried over magnesium sulphate
  5. customevaporated

출처 및 근거

ORD 기록
ord-dd964b479a76481eb7019da5d42ba403
출처 데이터셋
uspto-grants-1992_10
특허 번호
US05158946

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