Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(benzenesulfonylaminomethyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891531노트

반응식

HRID 891531 반응식
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([CH2:14][NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:18])=[O:17])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:46]2[C@H:47]([CH3:70])[C@H:48]3[C@@H:65]([C@H:66]([OH:68])[CH3:67])[C:64](=[O:69])[N:49]3[C:50]=2[C:51]([O:53][CH2:54][C:55]2[CH:60]=[CH:59][C:58]([N+:61]([O-:63])=[O:62])=[CH:57][CH:56]=2)=[O:52])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.C(OCC)(=O)C>[C:19]1([S:16]([NH:15][CH2:14][C:12]2[N:13]=[C:9]([N:7]3[CH2:8][CH:5]([S:4][C:46]4[C@H:47]([CH3:70])[C@@H:48]5[C@@H:65]([C@H:66]([OH:68])[CH3:67])[C:64](=[O:69])[N:49]5[C:50]=4[C:51]([O:53][CH2:54][C:55]4[CH:56]=[CH:57][C:58]([N+:61]([O-:63])=[O:62])=[CH:59][CH:60]=4)=[O:52])[CH2:6]3)[S:10][CH:11]=2)(=[O:17])=[O:18])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

참가 물질

9

반응물 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 222428723-Acetylthio-1-[4-(benzenesulfonylamino)methyl-1,3-thiazol-2-yl]azetidineHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

생성물 1

HCID 131725347p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(benzenesulfonylaminomethyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate수율 61.5%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-acetylthio-1-[4-(benzenesulfonylaminomethyl)-1,3-thiazol-2-yl]azetidine (1.00 g, 2.68 mmol) (obtained as described in Reference Example 65) in dimethylformamide (30 ml) was added hydrazine acetate (296 mg, 3.21 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.75 g, 2.94 mmol) in acetonitrile (60 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (1.87 ml, 10.7 mmol). The mixture was stirred for 3 hours while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: hexane:ethyl acetate (1:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(benzenesulfonylaminomethyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.13 g, yield 61%) as a pale yellow solid.

후처리

  1. customthe completion of the reaction
  2. stirringThe mixture was stirred for 3 hours
  3. additionwere added to the reaction mixture
  4. stirringThe resulting mixture was shaken in a separatory funnel
  5. customthe ethyl acetate layer was separated
  6. washwashed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column (eluant: hexane:ethyl acetate (1:1))

출처 및 근거

ORD 기록
ord-1d8ee47cf4d243c1858472be609963f6
출처 데이터셋
uspto-grants-2006_02
특허 번호
US07001897B2

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