4-Methylmorpholine → HCID 11596946, compound

HRID 2367079Notes

Reaction equation

HRID 2367079 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.C1C=NC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:64][C:65]1[CH:72]=[CH:71][C:68]([CH2:69][NH2:70])=[CH:67][CH:66]=1>CN(C)C=O>[Cl:64][C:65]1[CH:72]=[CH:71][C:68]([CH2:69][N:70]2[C:16](=[O:18])[C:15]3[C:14](=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]2([C:9]2[CH:10]=[CH:11][C:5]3[O:4][CH2:3][C:2](=[O:1])[NH:7][C:6]=3[CH:8]=2)[OH:13])=[CH:67][CH:66]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 660364-ChlorobenzylamineHCID 181649HOAtHCID 17174602-(3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 11596946HCID 11596946, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-yl)carbonylbenzoic acid (50 mg, 0.17 mmol) in N,N-dimethylformamide (1.00 mL) was added N-methylmorpholine (74 uL, 0.67 mmol) followed by addition of HOAt (55 mg, 0.40 mmol) and HATU (130 mg, 0.34 mmol). The mixture was stirred for 30 minutes at room temperature followed by the addition of 4-chloro-benzylamine (49 uL, 0.40 mmol). The reaction mixture was then heated to 60° C. for 2 h. The mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in ethyl acetate and the organic layer was washed with brine, 1.0 M aq. hydrochloric acid, brine, saturated aq. sodium-hydrogencarbonate and brine. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated in vacuo. The residue was recrystallized from methanol to afford the title compound (7.3 mg, 15%). MS (EI) for C22H15ClN2O4: 443 (MNa+).

Workup

  1. temperatureThe reaction mixture was then heated to 60° C. for 2 h
  2. temperatureThe mixture was cooled to room temperature
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washthe organic layer was washed with brine, 1.0 M aq. hydrochloric acid, brine, saturated aq. sodium-hydrogencarbonate and brine
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated in vacuo
  10. customThe residue was recrystallized from methanol

Sources & evidence

ORD record
ord-c8d2739b70354789ad39a255cd56921e
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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