Hydrochloric Acid → HCID 44137813, compound

HRID 2380953Notes

Reaction equation

HRID 2380953 reaction equation
[Cl:1][C:2]1[C:3]([N:33]=C(C2C=CC=CC=2)C2C=CC=CC=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:23](=[O:24])[C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[CH:21][NH:20][CH:19]=2)=[O:17])=[CH:11][C:10]=1[F:32].C(=O)([O-])[O-].[K+].[K+].[P:53]([O:65]CCl)([O:60]C(C)(C)C)([O:55][C:56](C)(C)C)=[O:54].Cl>CN(C=O)C.CCOC(C)=O.CCO.O>[P:53]([OH:65])([OH:60])([O:55][CH2:56][N:20]1[CH:21]=[C:22]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:23](=[O:24])[C:18]([C:16](=[O:17])[NH:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([NH2:33])[C:2]=3[Cl:1])=[C:10]([F:32])[CH:11]=2)=[CH:19]1)=[O:54]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 86650689N-(4-((3-Chloro-2-((diphenylmethylene)amino)pyridin-4-yl)oxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

Product 1

HCID 44137813HCID 44137813, compoundYield 94%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide (5.0 g, 7.90 mmol) in DMF (50 mL) at room temperature were added potassium carbonate (7.64 g, 55.3 mmol) and di-tert-butyl chloromethyl phosphate (9.19 g, 35.5 mmol, see: PCT WO 2005/090367). The reaction mixture was stirred at room temperature for 2 days. The mixture was then diluted with EtOAc (250 mL), washed with water (200 mL), aq 10% LiCl (3×250 mL), dried over Na2SO4, and filtered. The filtrate was concentrated to give a residue, which was dissolved in EtOH (160 mL). To this stirred solution, was added water (60 mL), followed by the slow addition of conc. HCl (40 mL). The resulting mixture was stirred at rt for 15 min, and then allowed to stand overnight. HPLC analysis indicated that the reaction was complete. The solid was collected by filtration, rinsed with 50% EtOH/H2O (5×), water, EtOH, and EtOAc. The solid was dried under vacuum to give the title compound (4.3 g, 93%) as a white solid. 1H NMR (TFA-d) δ 9.60 (s, 1H), 8.79 (s, 1 H), 7.80-7.90 (m, 2H), 7.65-7.75 (m, 2H), 7.57 (d, 1H, J=7.04 Hz), 7.45 (t, 1H, J=6.80 Hz), 7.25-7.33 (m, 2H), 6.50 (d, 1H, J=5.92 Hz), 6.39 (d, 2H, J=9.88 Hz); MS (ESI+) m/z 579 (M+H)+.

Workup

  1. washwashed with water (200 mL), aq 10% LiCl (3×250 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give a residue, which
  6. stirringThe resulting mixture was stirred at rt for 15 min
  7. waitto stand overnight
  8. filtrationThe solid was collected by filtration
  9. washrinsed with 50% EtOH/H2O (5×), water, EtOH, and EtOAc
  10. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-8d75aabb86074288ac035d5ca40e20b7
Source dataset
uspto-grants-2012_09
Patent number
US08258118B2

Reaction notes

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