Toluene → HCID 5276327, compound

HRID 2415683Notes

Reaction equation

HRID 2415683 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=O)[C:18]3[C:13]4=[C:14]([O:28][CH2:29][CH2:30][N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:52])=CC=1.C1(C)C=CC=CC=1>ClC(Cl)C.C(Cl)Cl>[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[S:52])[C:18]3[C:13]4=[C:14]([O:28][CH2:29][CH2:30][N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 87949Lawesson's reagentHCID 3251421Potassium bis(trimethylsilyl)amideHCID 9933644HCID 9933644, compound

Product 1

HCID 5276327HCID 5276327, compoundYield 3.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of N-(4-Chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide (1.20 g, 2.64 mmol) of preparation 6 is dissolved in dichloroethane (160 mL) followed by the addition of KHMDS (0.5 M, 5.3 mL, 2.64 mmol, 1 equiv.). Then Lawesson's reagent (2.1 g, 5.28 mmol, 2.0 equiv) and toluene (160 mL) is added and the resulting mixture is heated at reflux for 24 h. The reaction is cooled to room temperature, diluted with DCM, washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, 1/4, 0/1 then DCM/MeOH 19/1) and then repurified by silica gel chromatography (DCM/MeOH 11/0, 45/1, 9/1) to afford 48 mg of the title compound as a solid.

Workup

  1. temperaturethe resulting mixture is heated
  2. temperatureat reflux for 24 h
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, 1/4, 0/1
  8. customDCM/MeOH 19/1) and then repurified by silica gel chromatography (DCM/MeOH 11/0, 45/1, 9/1)

Sources & evidence

ORD record
ord-a5cd27073e6a4d9eaf553de7883d19cd
Source dataset
uspto-grants-2004_11
Patent number
US06821969B2

Reaction notes

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