Triethylamine → HCID 11999115, compound

HRID 2102753Notes

Reaction equation

HRID 2102753 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][N:2]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])C.[Cl:34][C:35]1[CH:43]=[C:42]2[C:38]([C:39]([CH2:51][C:52]3[CH:57]=[CH:56][CH:55]=[C:54]([Cl:58])[CH:53]=3)([CH:45]3CCCNC3)[C:40](=[O:44])[NH:41]2)=[CH:37][CH:36]=1>C1(C)C=CC=CC=1.ClCCl>[Cl:34][C:35]1[CH:43]=[C:42]2[C:38]([C:39]([CH2:51][C:52]3[CH:57]=[CH:56][CH:55]=[C:54]([Cl:58])[CH:53]=3)([CH:45]3[CH2:31][CH2:30][N:29]([C:7]([C:4]4[CH:5]=[CH:6][N:1]=[N:2][CH:3]=4)=[O:9])[CH2:32][CH2:33]3)[C:40](=[O:44])[NH:41]2)=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 2761046Pyridazine-4-carboxylic AcidHCID 57803070Rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one

Product 1

HCID 11999115HCID 11999115, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of pyridazine-4-carboxylic acid (0.37 g, 3 mmol) (Aldrich) in toluene (15 mL) was added diphenylphosphoryl azide (0.958 g, 3.5 mmol) (Aldrich), followed by the addition of triethylamine (0.35 g, 3.6 mmol) (Aldrich). The mixture was stirred at room temperature for 30 minutes and the mixture became clear. Then the mixture was heated at 80° C. for 2 hours. After cooling to room temperature, the crude (0.8 mL, 0.16 mmol) was added to a solution of rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one (50 mg, 0.13 mmol) (from Example 25a supra) in dichloromethane (3 mL), followed by the addition of triethylamine (46 ul, 0.32 mmol) (Aldrich). The mixture was stirred at room temperature for 30 minutes. The mixture was partitioned between dichlormethane and water. The aqueous layer was extracted with dichlormethane. The combined organic layer was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by chromatography to give rac-6-chloro-3-(3-chloro-benzyl)-3-{1-(pyridazine-4-carbonyl)-piperidin-4-yl}-1,3-dihydro-indol-2-one as fraction one and a white solid. (Yield 32 mg, 50%).

Workup

  1. temperatureThen the mixture was heated at 80° C. for 2 hours
  2. temperatureAfter cooling to room temperature
  3. stirringThe mixture was stirred at room temperature for 30 minutes
  4. customThe mixture was partitioned between dichlormethane and water
  5. extractionThe aqueous layer was extracted with dichlormethane
  6. washThe combined organic layer was washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-8b7c410cdcc444a8a563602e15361daf
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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