Phosgene → HCID 53310623, compound

HRID 59036Notes

Reaction equation

HRID 59036 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:17]([O-])(O)=[O:18].[Na+].C(Cl)(Cl)=O.[NH2:26][C:27]1[CH:44]=[CH:43][C:30]([O:31][C:32]2[CH:37]=[CH:36][N:35]=[C:34]3[NH:38][C:39](=[O:42])[N:40]([CH3:41])[C:33]=23)=[CH:29][C:28]=1[F:45]>C(Cl)Cl.C1(C)C=CC=CC=1.C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:17]([NH:26][C:27]2[CH:44]=[CH:43][C:30]([O:31][C:32]3[CH:37]=[CH:36][N:35]=[C:34]4[NH:38][C:39](=[O:42])[N:40]([CH3:41])[C:33]=34)=[CH:29][C:28]=2[F:45])=[O:18])[N:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 7706343-tert-butyl-1-phenyl-1H-pyrazol-5-amineHCID 441849547-(4-Amino-3-fluorophenoxy)-1-N-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

Product 1

HCID 53310623HCID 53310623, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-Tert-butyl-1-phenyl-1H-pyrazol-5-amine (550 mg, 1.8 mmol) was dissolved in CH2Cl2 (25 mL) and an equal volume of saturated NaHCO3 (aq) was added. The biphasic mixture was stirred and cooled to 0° C. with an ice/water bath. After 10 minutes, 2 equiv. of a 1.9 M solution of phosgene in toluene were added. The mixture was vigorously stirred for 10 minutes, the organic layer was isolated, washed with H2O, dried (MgSO4) and concentrated to about 5 mL. This solution was added to a solution of the 7-(4-amino-3-fluorophenoxy)-1-N-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (8a) (200 mg, 1.4 mmol) in THF. The solution was stirred for 15 hours at room temperature, the solvents were evaporated and the solid residue was washed with Et2O and CH2Cl2 to afford the title compound as a white solid.

Workup

  1. stirringThe mixture was vigorously stirred for 10 minutes
  2. customthe organic layer was isolated
  3. washwashed with H2O
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated to about 5 mL
  6. stirringThe solution was stirred for 15 hours at room temperature
  7. customthe solvents were evaporated
  8. washthe solid residue was washed with Et2O and CH2Cl2

Sources & evidence

ORD record
ord-3e28915f1d7b44e8a880714944422007
Source dataset
uspto-grants-2016_09
Patent number
US09439893B2

Reaction notes

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