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

HRID 2080248ノート

反応式

HRID 2080248 の反応式
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

参加物

11

反応物 7

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

生成物 1

HCID 58387856Cinnoline-6-carboxylic acid 3-phenoxy-benzylamide収率 11%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e7bad04937ef47398deef65e560fd25f
出典データセット
uspto-grants-2011_04
特許番号
US07932272B2

反応ノート

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