4-Methylmorpholine → HCID 25242441, compound

HRID 2367098Notes

Reaction equation

HRID 2367098 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]([C:14]3[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=3[C:16]([OH:18])=O)=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.CN1CCOCC1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.O[NH:64][C:65]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[NH:66].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(#N)C.CN(C=O)C>[C:67]1([C:65]2[N:66]=[C:16]([C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[C:12]([C:9]3[CH:10]=[CH:11][C:5]4[O:4][CH2:3][C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)=[O:13])[O:18][N:64]=2)[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 17174602-(3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonyl)benzoic acidHCID 2724141Tetrabutylammonium FluorideHCID 2724699PyBOPHCID 178513281HCID 178513281, compound

Product 1

HCID 25242441HCID 25242441, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-[(3-Oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]benzoic acid (100 mg, 0.34 mmol.) was taken into DMF (1 mL) followed by addition of 4-methylmorpholine (75 uL, 0.7 mmol.) and PyBOP (177 mg, 0.34 mmol.) and the resulting solution was stirred for 15 minutes at room temperature. N-Hydroxybenzenecarboximidamide (46 mg, 0.34 mmol.) was added to the solution thus obtained and the mixture was allowed to stir an additional hour then partitioned with ethyl acetate and water. The organic layer was washed with water (3×), 10% aqueous citric acid (2×), saturated aqueous sodium bicarbonate (1×) and brine then dried over anhydrous sodium sulfate. Filtration and concentration afforded a crystalline solid that was suspended in anhydrous 1:1 THF: acetonitrile (1 mL) followed by addition of 1M TBAF in THF (300 uL) and the mixture was allowed to stir at room temperature under a nitrogen atmosphere for 24 hours. The solvent was removed in vacuo and the residue partitioned with ethyl acetate and water. The organic layer was washed twice with additional water and a crystalline solid was obtained from the organic layer. The solid product was collected by filtration and suspended in methanol. The solid was again collected by filtration, washed with additional methanol and dried in vacuo to give 6-{[2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one (63 mg, 47% yield) as a white crystalline solid. 1H NMR (400 MHz, d4-MeOH): 8.26 (d, 1H), 7.91 (d, 2H), 7.83-7.80 (m, 2H), 7.62 (d, 1H), 7.52-7.44 (m, 4H), 7.35 (dd, 1H), 6.96 (d, 1H), 4.61 (s, 2H). MS (EI) for C23H15N3O4: 398 (MH+).

Workup

  1. customthus obtained
  2. stirringto stir an additional hour
  3. customthen partitioned with ethyl acetate and water
  4. washThe organic layer was washed with water (3×), 10% aqueous citric acid (2×), saturated aqueous sodium bicarbonate (1×) and brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationFiltration and concentration
  7. customafforded a crystalline solid
  8. stirringto stir at room temperature under a nitrogen atmosphere for 24 hours
  9. customThe solvent was removed in vacuo
  10. customthe residue partitioned with ethyl acetate and water
  11. washThe organic layer was washed twice with additional water
  12. customa crystalline solid was obtained from the organic layer
  13. filtrationThe solid product was collected by filtration
  14. filtrationThe solid was again collected by filtration
  15. washwashed with additional methanol
  16. customdried in vacuo

Sources & evidence

ORD record
ord-c070ed4aff624c4eb4131e9026298ce3
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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