1,2-Oxazole-5-carboxylic acid → N-[[3-[1,2,3,4,4a,5-hexahydro-3-(5 isoxazolylcarbonyl)pyrazino[2,1-c][1,4]benzoxazin-8-yl]-2-oxo-5-(S)-oxazolidinyl]methyl]-acetamide

HRID 618781Notes

Reaction equation

HRID 618781 reaction equation
C1(CO[C:9]([N:11]2[CH2:20][CH2:19][N:18]3[CH:13]([CH2:14][O:15][C:16]4[CH:24]=[C:23]([N:25]5[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]5=[O:35])[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])C=CC=CC=1.[O:36]1[C:40](C(O)=O)=[CH:39][CH:38]=[N:37]1.Cl.C(N=C=NCCCN(C)C)C>CO.C(Cl)Cl.[Pd].CN(C)C1C=CN=CC=1>[O:36]1[C:40]([C:9]([N:11]2[CH2:20][CH2:19][N:18]3[CH:13]([CH2:14][O:15][C:16]4[CH:24]=[C:23]([N:25]5[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]5=[O:35])[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])=[CH:39][CH:38]=[N:37]1

Participants

8

Reactant 3

HCID 20605991,2-Oxazole-5-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 158700138-[5-(S)-[(Acetylamino)methyl]-2-oxo-3-oxazolidinyl]-1,2,4a,5-tetrahydropyrazino[2,1-c][1,4]benzoxazine-3(4H)-carboxylic acid phenylmethyl ester

Product 1

HCID 10411030N-[[3-[1,2,3,4,4a,5-hexahydro-3-(5 isoxazolylcarbonyl)pyrazino[2,1-c][1,4]benzoxazin-8-yl]-2-oxo-5-(S)-oxazolidinyl]methyl]-acetamide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a flask containing 8-[5-(S)-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-1,2,4a, 5-tetrahydropyrazino[2,1-c][1,4]benzoxazine-3(4H)-carboxylic acid phenylmethyl ester (EXAMPLE 1, 150 mg, 0.31 mmol) in methanol (5 mL) and methylene chloride (5 mL) is introduced 10% palladium on carbon (70 mg). The mixture is placed under a hydrogen balloon for 17 hours, filtered through celite, and concentrated in vacuo. The residue is dissolved in pyridine (5 mL) followed by the addition of isoxazole-5-carboxylic acid (40 mg, 0.35 mmol), 4-dimethylaminopyridine (5 mg, 0.04 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(70 mg, 0.35 mmol). The reaction is stirred under an inert atmosphere for 17 hours, diluted with methylene chloride (20 mL), washed with 1N HCl (20 mL) and saline, dried over Na2SO4, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with chloroform/methanol (97/3). The appropriate fractions are combined (Rf =0.42, TLC, chloroform/methanol, 90/10) and concentrated in vacuo to give the title compound, HRMS calcd for C21H23N5O6 : 441.1648. Found: 441.1658.

Workup

  1. customfor 17 hours
  2. filtrationfiltered through celite
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue is dissolved in pyridine (5 mL)
  5. washwashed with 1N HCl (20 mL) and saline
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customchromatographed on silica gel (230-400 mesh, 100 mL)
  9. washeluting with chloroform/methanol (97/3)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5a1e78f866dc49389eae17347515968e
Source dataset
uspto-grants-1999_09
Patent number
US05955460

Reaction notes

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