Phenyl isocyanate → HCID 22050706, compound

HRID 1867151Notes

Reaction equation

HRID 1867151 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.[C:43]1([N:49]=[C:50]=[O:51])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>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:50]([NH:49][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:51]

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 79724-MethylmorpholineHCID 22051057HCID 22051057, compound

Product 1

HCID 22050706HCID 22050706, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a cooled (0° C.) solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3-chloro-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one trifluoroacetate (0.25 g, 0.48 mmol) in DMA (2.0 mL) was added 4-methylmorpholine (0.06 mL, 0.53 mmol) and phenyl isocyanate (0.06 mL, 0.53 mmol). The reaction was stirred at RT for 1.5 h. Solvent distilled and 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 (0.18 g, 71%). 1H NMR (CD3OD/400 MHz) δ7.60 (m, 1H), 7.54 (m, 1H), 7.33 (d, 2H, J=7.6 Hz), 7.22 (m, 5H), 7.06 (m, 1H), 6.95 (t, 1H, J=7.2 Hz), 6.73 (s, 1H), 5.44 (s, 2H), 4.53 (s, 2H), 2.07 (s, 3H). ESHRMS m/z 528.1304 (M+H calculated for C27H22ClF3N3O3 requires 528.1296).

Workup

  1. distillationSolvent distilled
  2. customcrude product purified by preparatory HPLC
  3. customAcetonitrile was evaporated
  4. washthe solution washed with 5% NaHCO3 (30 mL)
  5. extractionextracted in DCM (3×25 mL)
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a white solid
  9. customdried in vacuo (0.18 g, 71%)

Sources & evidence

ORD record
ord-e12d1b875a124f8194f1bbde0dc5ffee
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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