Methyl chloroformate → HCID 22050371, compound

HRID 1867147Notes

Reaction equation

HRID 1867147 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:11]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[N:17]([C:21]2[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:24]([O:26][CH3:27])=[O:25])[C:16](=[O:32])[CH:15]=1.CN1CCOCC1.Cl[C:46]([O:48][CH3:49])=[O:47]>CC(N(C)C)=O>[F:37][C:35]1[CH:34]=[CH:33][C:11]([CH2:12][O:13][C:14]2[CH:19]=[C:18]([CH3:20])[N:17]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:24]([O:26][CH3:27])=[O:25])[C:16](=[O:32])[CH:15]=2)=[C:10]([CH2:9][NH:8][C:46]([O:48][CH3:49])=[O:47])[CH:36]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 22050495methyl 3-[4-([2-(aminomethyl)-4-fluorobenzyl]oxy)-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoate trifluoroacetate

Product 1

HCID 22050371HCID 22050371, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a cooled (0° C.) solution of methyl 3-[4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoate trifluoroacetate (from Step 2) (0.50 g, 0.95 mmol) in DMA (4 mL) was added 4-methylmorpholine (0.21 mL, 1.9 mmol) and methyl chloroformate (0.08 mL, 1.0 mmol). Reaction was stirred at RT for 1 h. Solvent removed by distillation. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO3 (30 mL) and extracted in DCM (3×25 mL). The organic extracts were dried over Na2SO4, filtered, and concentrated to a white solid, dried in vacuo (0.36 g, 81%). 1H NMR (CD3OD/400 MHz) δ8.03 (m, 1H), 7.77 (s, 1H), 7.53 (d, 1H, J=7.6 Hz), 7.47 (m, 1H), 7.12 (m, 1H), 7.03 (m, 1H), 6.21 (s, 1H), 6.08 (s, 1H), 5.18 (s, 2H), 4.38 (s, 2H), 3.89 (s, 3H), 3.65 (s, 3H), 2.12 (s, 3H), 1.89 (s, 3H). ESHRMS m/z 469.1767 (M+H calculated for C25H26FN2O6 requires 469.1769).

Workup

  1. customReaction
  2. customSolvent removed by distillation
  3. customCrude product purified by preparatory HPLC
  4. customAcetonitrile was evaporated
  5. washthe solution washed with 5% NaHCO3 (30 mL)
  6. extractionextracted in DCM (3×25 mL)
  7. dry with materialThe organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a white solid
  10. customdried in vacuo (0.36 g, 81%)

Sources & evidence

ORD record
ord-eb65c6e9a0674cfc8ad370196c8695ae
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

Loading…