HCID 53465552, compound → HCID 136000178, compound

HRID 2280255Notes

Reaction equation

HRID 2280255 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:19]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[CH:18][N:17]([CH2:26][CH2:27][F:28])[N:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1>CCOC(C)=O.CCO.[Pd]>[F:28][CH2:27][CH2:26][N:17]1[CH:18]=[C:19]([C:20]2[CH:21]=[CH:22][N:23]=[CH:24][CH:25]=2)[C:15]([C:12]2[CH:13]=[CH:14][C:9]([OH:8])=[CH:10][CH:11]=2)=[N:16]1

Participants

4

Reactant 1

HCID 53465552HCID 53465552, compound

Product 1

HCID 136000178HCID 136000178, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584252Ethanol ethylacetateSolvent

Procedure

Pd/C (1 g) was added to a solution of Intermediate 3B, 4-(3-(4-(benzyloxy)phenyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyridine (2.1 g) in EtOAc/EtOH (30 mL+30 mL). The mixture was stirred in autoclave at 2.5 atm H2 for 18 h. Pd/C was filtered off and the filtrate was concentrated under reduced pressure to yield the crude product. Purification by flash column chromatography afforded the pure product, 4-(1-(2-fluoroethyl)-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenol (1.46 g, 92%). 1H NMR (300 MHz, methanol-d4) δ 8.37 (dd, J=4.6, 1.6, 2H), 8.08 (s, 1H), 7.31 (dd, J=4.6, 1.7, 2H), 7.27-7.22 (m, 2H), 6.83-6.78 (m, 2H), 4.81 (dt, J=47.1, 4.7, 2H), 4.49 (dt, J=26.6, 4.7, 2H). MS (DCI—NH3) m/z=284 (M+H)+. (Note: Alternative preparation experimental details published in Journal of Medicinal Chemistry 2011, 54, 5820-5835, Compound 8b)

Workup

  1. filtrationPd/C was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto yield the crude product
  4. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-33ce3bc4fbf94195b5a06a8ebaf412fd
Source dataset
uspto-grants-2015_09
Patent number
US09138494B2

Reaction notes

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