Triethylamine → N-1H-pyrrolo[2,3-b]pyridin-6-yl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene) piperidine-1-carboxamide

HRID 1666340Notes

Reaction equation

HRID 1666340 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8](NC(=O)OC3C=CC=CC=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1.Cl.[NH:21]1[CH2:26][CH2:25][C:24](=[CH:27][C:28]2[CH:29]=[C:30]([CH:42]=[CH:43][CH:44]=2)[O:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][N:33]=2)[CH2:23][CH2:22]1.C([N:47]([CH2:50]C)CC)C.CC[O:54]C(C)=O>CS(C)=O.C(OCC)C>[NH:1]1[C:5]2=[N:6][C:7]([NH:47][C:50]([N:21]3[CH2:26][CH2:25][C:24](=[CH:27][C:28]4[CH:44]=[CH:43][CH:42]=[C:30]([O:31][C:32]5[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:39])[F:40])=[CH:34][N:33]=5)[CH:29]=4)[CH2:23][CH2:22]3)=[O:54])=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66833838Phenyl 1H-pyrrolo[2,3-b]pyridin-5-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 66875876N-1H-pyrrolo[2,3-b]pyridin-6-yl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene) piperidine-1-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of phenyl 1H-pyrrolo[2,3-b]pyridin-5-ylcarbamate (0.150 g, 0.60 mmol, from Step 1) in DMSO (5 mL) was added 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.22 g, 0.60 mmol) (from Example 1, Step 5), followed by the addition of triethylamine (0.17 mL, 1.2 mmol). The reaction mixture was stirred at 60° C. overnight. The reaction mixture was cooled down and EtOAc (30 mL) was added. The organic layer was washed with water, saturated NH4Cl, and brine, dried over Na2SO4, filtered and concentrated. Purification by column chromatography (0-5% MeOH/CH2Cl2) gave a foam. Diethyl ether was added and a precipitate formed which was collected by filtration to give the title compound (208 mg). MS (M+1): 494.19; 1H NMR (400 MHz, DMSO-d6) δ ppm 11.38-11.40 (m, 1H) 8.54-8.56 (m, 1H) 8.46-8.49 (m, 1H) 8.20 (dd, 1H) 8.15 (d, 1H) 7.92-7.94 (m, 1H) 7.34-7.42 (m, 2H) 7.21 (d, 1H) 7.11-7.15 (m, 1H) 7.02-7.06 (m, 2H) 6.37-6.40 (m, 1H) 6.31-6.34 (m, 1H) 3.55 (t, 2H) 3.47 (t, 2H) 3.28-3.30 (m, 1H) 2.50-2.51 (m, 1H) 2.34 (t, 2H).

Workup

  1. temperatureThe reaction mixture was cooled down
  2. washThe organic layer was washed with water, saturated NH4Cl, and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by column chromatography (0-5% MeOH/CH2Cl2)
  7. customgave a foam
  8. customa precipitate formed which
  9. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-a1ef8a0cc90a483ab87593e0140ddabf
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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