2,4-Dinitrophenol → 7-[o-(N-Butoxycarbonyl-N-methylaminomethyl)phenylacetamido]-3-[2-(2-carboxyethyl)-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl]-3-cephem-4-carboxylic acid

HRID 2049863

반응식

HRID 2049863 반응식
[NH2:1][CH:2]1[C:29](=[O:30])[N:4]2[C:5]([C:26]([OH:28])=[O:27])=[C:6]([CH2:9][S:10][C:11]3[CH:12]=[CH:13][C:14]4[N:15]([C:17](=[O:25])[N:18]([CH2:20][CH2:21][C:22]([OH:24])=[O:23])[N:19]=4)[N:16]=3)[CH2:7][S:8][C@H:3]12.[C:31]([O:35][C:36]([N:38]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH2:47][C:48]([O:50]C1C=CC([N+]([O-])=O)=CC=1[N+]([O-])=O)=O)[CH3:39])=[O:37])([CH3:34])(C)C.[C:63](OC(N(CC1C=CC=CC=1CC(O)=O)C)=O)(C)(C)[CH3:64].[N+](C1C=C([N+]([O-])=O)C=CC=1O)([O-])=O.C1CCC(N=C=NC2CCCCC2)CC1>C(#N)C.C1COCC1.C(N(CC)CC)C>[CH2:31]([O:35][C:36]([N:38]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH2:47][C:48]([NH:1][CH:2]1[C:29](=[O:30])[N:4]2[C:5]([C:26]([OH:28])=[O:27])=[C:6]([CH2:9][S:10][C:11]3[CH:12]=[CH:13][C:14]4[N:15]([C:17](=[O:25])[N:18]([CH2:20][CH2:21][C:22]([OH:24])=[O:23])[N:19]=4)[N:16]=3)[CH2:7][S:8][C@H:3]12)=[O:50])[CH3:39])=[O:37])[CH2:34][CH2:63][CH3:64]

참가 물질

9

반응물 5

HCID 14932,4-DinitrophenolHCID 10868DicyclohexylcarbodiimideHCID 20344367o-(N-t-butoxycarbonyl-N-methylaminomethyl)phenylacetic acidHCID 203443712,4-dinitrophenyl o-(N-t-butoxycarbonyl-N-methylaminomethyl)phenylacetateHCID 1317110707-Amino-3-[2-(2-carboxyethyl)-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl]-3-cephem-4-carboxylic acid

생성물 1

HCID 1317110697-[o-(N-Butoxycarbonyl-N-methylaminomethyl)phenylacetamido]-3-[2-(2-carboxyethyl)-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl]-3-cephem-4-carboxylic acid수율 50%

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

실험 절차

To a mixture of 7-amino-3-[2-(2-carboxyethyl)-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl]-3-cephem-4-carboxylic acid (452 mg., 1 m.mole) and triethylamine (0.46 ml., 3.3 m.mole) in 50% aqueous acetonitrile (4 ml.) was added a THF solution (3 ml.) of 2,4-dinitrophenyl o-(N-t-butoxycarbonyl-N-methylaminomethyl)phenylacetate prepared from o-(N-t-butoxycarbonyl-N-methylaminomethyl)phenylacetic acid (283 mg., 1.1 m.mole), 2,4-dinitrophenol (202 mg., 1.1 m.mole) and DCC (227 mg., 1.1 m.mole). The mixture was stirred at room temperature overnight and concentrated under reduced pressure to remove the organic solvents. The aqueous concentrate was washed with ether (3×20 ml.), acidified with c.HCl to pH 1-2 and extracted with ethyl acetate (5×20 ml.). The combined extracts were dried with anhydrous Na2SO4 and evaporated to dryness. The residue was chromatographed on a column of silica gel (Wako gel, C-200, 10 g.) by eluting with a mixture of MeOH-CHCl3 (MeOH: 0 to 3%). The combined eluates which contained the desired product were evaporated to give 359 mg. (50%) of the title compound. M.p.>150° C. (dec.).

후처리

  1. concentrationconcentrated under reduced pressure
  2. customto remove the organic solvents
  3. concentrationThe aqueous concentrate
  4. washwas washed with ether (3×20 ml.)
  5. extractionHCl to pH 1-2 and extracted with ethyl acetate (5×20 ml.)
  6. dry with materialThe combined extracts were dried with anhydrous Na2SO4
  7. customevaporated to dryness
  8. customThe residue was chromatographed on a column of silica gel (Wako gel, C-200, 10 g.)
  9. washby eluting with a mixture of MeOH-CHCl3 (MeOH: 0 to 3%)
  10. customwere evaporated
  11. customto give 359 mg

출처 및 근거

ORD 기록
ord-1a3f451584494e3bae772faeefb51bda
출처 데이터셋
uspto-grants-1980_04
특허 번호
US04198506

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