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 467380노트

반응식

HRID 467380 반응식
[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

참가 물질

7

반응물 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

생성물 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-carboxylate수율 69.6%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f9dd2f026a8147e3a2a8ad193745dbcb
출처 데이터셋
uspto-grants-1992_10
특허 번호
US05158946

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