Triethylamine → HCID 11999359, compound

HRID 2102769Notes

Reaction equation

HRID 2102769 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([OH:13])=O)=[CH:7][N:6]=1)=[O:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.[Cl:38][C:39]1[CH:47]=[C:46]2[C:42]([C:43]([CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[C:58]([Cl:62])[CH:57]=3)([CH:49]3[CH2:54][CH2:53][CH2:52][NH:51][CH2:50]3)[C:44](=[O:48])[NH:45]2)=[CH:41][CH:40]=1>C1(C)C=CC=CC=1.ClCCl>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:51]2[CH2:52][CH2:53][CH2:54][CH:49]([C:43]3([CH2:55][C:56]4[CH:61]=[CH:60][CH:59]=[C:58]([Cl:62])[CH:57]=4)[C:42]4[C:46](=[CH:47][C:39]([Cl:38])=[CH:40][CH:41]=4)[NH:45][C:44]3=[O:48])[CH2:50]2)=[O:13])=[CH:7][N:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 5796316-(Methoxycarbonyl)pyridine-3-carboxylic acidHCID 57803070Rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one

Product 1

HCID 11999359HCID 11999359, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of pyridine-2,5-dicarboxylic acid-2-methyl ester (0.54 g, 3.0 mmol) (from Example 83 a supra) 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 0.5 hour and the mixture became clear. Then the mixture was heated at 80° C. for 2 hours. After cooling to room temperature, the crude (0.21 mL, 0.38 mmol) was added to a solution of rac-6-chloro-3-(3-chloro-benzyl)-3-piperidin-3-yl-1,3-dihydro-indol-2-one (120 mg, 0.32 mmol) (from Example 25a supra) in dichloromethane (3 mL), followed by the addition of triethylamine (0.11 mL, 0.80 mmol) The mixture was stirred at room temperature for 0.5 hour. The mixture was partitioned between dichlormethane and water. The aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by chromatography to give rac-5-{3-[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-piperidine-1-carbonyl}-pyridine-2-carboxylic acid methyl ester as a white solid. (Yield 65 mg, 36.5%).

Workup

  1. temperatureThen the mixture was heated at 80° C. for 2 hours
  2. temperatureAfter cooling to room temperature
  3. stirringwas stirred at room temperature for 0.5 hour
  4. customThe mixture was partitioned between dichlormethane and water
  5. extractionThe aqueous layer was extracted with dichloromethane
  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-26897c5277af4c19ba3b1ec1e7ad56ce
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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