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 467370ノート

反応式

HRID 467370 の反応式
[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

参加物

6

反応物 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

生成物 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-carboxylate収率 64.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-dd964b479a76481eb7019da5d42ba403
出典データセット
uspto-grants-1992_10
特許番号
US05158946

反応ノート

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