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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 2082908
Notes
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Reaction equation

HRID 2082908 reaction equation
[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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 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

Product 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 acidYield 50%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

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 (3ml.) 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.).

Workup

  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

Sources & evidence

ORD record
ord-eee27760dad6443ab64705d9ea60c835
Source dataset
uspto-grants-1978_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04082912

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes