Hydrochloric Acid → Cinnoline-6-carboxylic acid 3-phenoxy-benzylamide

HRID 2080248Notes

Reaction equation

HRID 2080248 reaction equation
CO[C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[N:10][CH:9]=[CH:8]2)=[O:4].[OH-].[Na+].Cl.N1C=CC=CC=1OC[C:26]1[CH:43]=[CH:42][C:29]([CH2:30][NH:31]C(C2C(N)=NC(N)=CN=2)=O)=[CH:28][CH:27]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=2N=N1.C(N(CC)CC)C.FC(F)(F)C(O)=[O:81]>C(O)C.O.C1(C)C=CC=CC=1>[O:81]([C:43]1[CH:42]=[C:29]([CH:28]=[CH:27][CH:26]=1)[CH2:30][NH:31][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[N:10][CH:9]=[CH:8]2)=[O:4])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11298404Methyl Cinnoline-6-carboxylateHCID 58875320HCID 58875320, compound

Product 1

HCID 58387856Cinnoline-6-carboxylic acid 3-phenoxy-benzylamideYield 11%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of cinnoline-6-carboxylic acid methyl ester described in Preparation Example F-4 (16 mg, 0.085 mmol) in ethanol (1 mL) was added an aqueous solution of 1N sodium hydroxide (0.7 mL), and the solution was stirred at room temperature for 2 hours. 1N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, toluene was added, and the solution was concentrated in vacuo. To a solution of the obtained residue in N,N-dimethylformamide (2 mL) were added 4-phenoxybenzylamine described in Preparation Example 3 (17 mg, 0.085 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (48 mg, 0.108 mmol) and triethylamine (24 μl, 0.172 mmol), and the solution was stirred at room temperature for 14 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate, the organic layer was washed with an aqueous solution of saturated sodium bicarbonate, and then concentrated. The residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used), and the title compound (4.4 mg, 0.0093 mmol, 11%) was obtained as a trifluoroacetic acid salt.

Workup

  1. additionwas added
  2. concentrationthe solution was concentrated in vacuo
  3. additionTo a solution of the obtained residue in N,N-dimethylformamide (2 mL) were added 4-phenoxybenzylamine
  4. stirringthe solution was stirred at room temperature for 14 hours
  5. extractionwas extracted with ethyl acetate
  6. washthe organic layer was washed with an aqueous solution of saturated sodium bicarbonate
  7. concentrationconcentrated
  8. customThe residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used)

Sources & evidence

ORD record
ord-e7bad04937ef47398deef65e560fd25f
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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