Methanesulfonyl chloride → benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467380ノート

反応式

HRID 467380 の反応式
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])/[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.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[NH2:54][C@@H:55]1[C:86](=[O:87])[N:57]2[C:58]([C:70]([O:72][CH:73]([C:80]3[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=3)[C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)=[O:71])=[C:59]([CH2:62][S:63][C:64]3[CH2:68][O:67][C:66](=[O:69])[CH:65]=3)[CH2:60][S:61][C@H:56]12>CN(C)C=O.N1C=CC=CC=1>[O:69]=[C:66]1[CH:65]=[C:64]([S:63][CH2:62][C:59]2[CH2:60][S:61][C@@H:56]3[C@H:55]([NH:54][C:27](=[O:28])/[C:26](/[C:24]4[N:25]=[C:21]([NH:20][C:1]([C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)([C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)[S:22][CH:23]=4)=[N:30]\[O:31][CH2:32][C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[C:86](=[O:87])[N:57]3[C:58]=2[C:70]([O:72][CH:73]([C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)=[O:71])[CH2:68][O:67]1

参加物

7

反応物 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 13078701(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 67908483Diphenylmethyl 7beta-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate

生成物 1

HCID 141558981benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate収率 69.6%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒

実験手順

A stirred solution of 2-(2-tritylaminothiazol-4-yl)-2-(Z)-(t-butyloxycarbonyl)methoxyiminoacetic acid (498 mg) in dimethylformamide (4 ml) was cooled to -55° C. to -60° C. and N,N-diisopropylethylamine (0.157 ml) was added, followed by methanesulphonyl chloride (0.068 ml). The mixture was stirred at the same temperature for 0.5 h and then diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate (395 mg) and pyridine (0.064 ml) were added. The mixture was then stirred at 0° for 1.25 h, and then partitioned between ethyl acetate and 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 product (567 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel 1:1 going to 3:7 hexane: ethyl acetate as eluent). υmax (CHCl3) 3400, 3250, 1790, 1745, 1730 and 1680cm-1 ; δ(CDCl3) 1.43 (9H, s), 3.40 (1H, d, J 18.0Hz), 3.56 (1H, d, J 18.0Hz), 3.91 (1H, d, J 12.4Hz), 4.02 (1H, d, J 12.4Hz), 4.72 (2H, s), 4.73 (1H, d, J 17.1Hz), 4.81 (1H, d, J 17.1Hz), 5.08 (1H, d, J 4.9Hz), 5.66 (1H, s), 5.93 (1H, dd, J 4.9 and 8.3Hz), 6.82 (1H, s), 6.95 (1H, s,), 7.01 (1H, s), 7.2-7.45 (25H, m), 8.77 (1H, d, J 8.3Hz).

後処理

  1. stirringThe mixture was then stirred at 0° for 1.25 h
  2. custompartitioned between ethyl acetate and 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-f9dd2f026a8147e3a2a8ad193745dbcb
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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