4-Methylmorpholine → HCID 21035361, compound

HRID 1866993Notes

Reaction equation

HRID 1866993 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:11]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[N:17]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:16](=[O:29])[C:15]=1[Cl:30].CN1CCOCC1.[CH2:43]([O:45][C:46](Cl)=[O:47])[CH3:44]>CC(N(C)C)=O>[Cl:30][C:15]1[C:16](=[O:29])[N:17]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:18]([CH3:20])=[CH:19][C:14]=1[O:13][CH2:12][C:11]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:10]=1[CH2:9][NH:8][C:46](=[O:47])[O:45][CH2:43][CH3:44]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 22051057HCID 22051057, compound

Product 1

HCID 21035361HCID 21035361, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

To solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3-chloro-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one trifluoroacetate (0.3 g, 0.00057 mol) in dimethylacetamide (3.0 mL) was added N-methymorpholine (0.064 g, 0.00064 mol), followed by addition of ethylchloroformate (0.06 mL) and stirred at −10° C., for 30 min. The solvents were distilled in vacuo and the residue was purified by reverse-phase HPLC purification using 10-90% CH3CN/Water (30 min gradient) at a flow rate of 100 mL/min. The appropriate fractions (m/z=481 M+H) were combined and freeze-dried, and the residue was partitioned between 5% sod. bicarbonate (20 mL) and dichloromethane (20 mL). The organic phase was washed with water, dried (Na2SO4) and concentrated to dryness under reduced pressure, to afford the title compound as a white amorphous powder (0.15 g, 55%): 1H NMR (CD3OD/400 MHz) δ7.61 (m, 1H), 7.52 (m, 1H), 7.26 (˜t, 2H, J=8.4 Hz), 7.12 (dd, 1H) 7.05 (3d, 1H, J=2.4 Hz), 6.74 (s, 1H), 5.40 (s, 2H), 4.42 (s, 2H), 4.05 (q, 2H, J=7.2 Hz), 2.12 (s, 3H), and 1.21 (t, 3H, J=7.2 Hz); ES-HRMS m/z 481.1118 (M+H C23H21N2O4F3Cl requires 481.1136).

Workup

  1. distillationThe solvents were distilled in vacuo
  2. customthe residue was purified by reverse-phase HPLC purification
  3. custom10-90% CH3CN/Water (30 min gradient)
  4. customfreeze-dried
  5. customthe residue was partitioned between 5% sod
  6. washThe organic phase was washed with water
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-d449f01706d94999a3956c2228a4983e
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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