HCID 67092227, compound → HCID 67092285, compound

HRID 2074098Notes

Reaction equation

HRID 2074098 reaction equation
C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][CH:10]([N:12]3[C:16]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)=[CH:15][C:14]([C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[N:13]3)[CH2:9]2)C=CC=CC=1>CCOC(C)=O.CO.[Pd]>[F:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C:16]2[N:12]([CH:10]3[CH2:9][NH:8][CH2:11]3)[N:13]=[C:14]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH:15]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 1

HCID 67092227HCID 67092227, compound

Product 1

HCID 67092285HCID 67092285, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
57 °C

Procedure

To a flask charged with NH4CO2H (6.2 g, 98.4 mmol) was added MeOH (50 mL) and stirred to a solution, followed by addition of a solution of 4-[1-[1-(diphenylmethyl)azetidin-3-yl]-5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine (2.3 g, 4.85 mmol) in EtOAc (50 mL), and the mixture stirred to a homogenous solution. This was added to a second flask containing 10% Pd/C (0.84 g) in MeOH (100 mL) under N2, and the reaction mixture was heated to 57° C. under N2 for 5 hours. The mixture was cooled to room temperature and the solids removed by filtration through a GF/F filter set. The filtrate was concentrated and diluted with water (50 mL) and then saturated with NaOH. The emulsion was then extracted with CH2Cl2 (3×100 mL) followed by Et2O (4×100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (90:10:1 CH2Cl2/MeOH/NH4OH) to yield the title compound as a white solid, 0.892 g, 60%. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 8.61 (d, 2 H), 7.69 (d, 2 H), 7.06-7.14 (m, 2 H), 6.95-7.05 (m, 2 H), 6.42 (s, 1 H), 4.91-5.08 (m, 1 H), 4.29 (t, 2 H), 3.98 (s, 2 H), 3.61 (t, 2 H); m/z (APCI+) for C18H17N4F 309.2 (M+H)+.

Workup

  1. additionTo a flask charged with NH4CO2H (6.2 g, 98.4 mmol)
  2. stirringthe mixture stirred to a homogenous solution
  3. additionThis was added to a second flask
  4. temperatureThe mixture was cooled to room temperature
  5. customthe solids removed by filtration through a GF/F
  6. filtrationfilter set
  7. concentrationThe filtrate was concentrated
  8. additiondiluted with water (50 mL)
  9. extractionThe emulsion was then extracted with CH2Cl2 (3×100 mL)
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude residue was purified by flash chromatography (90:10:1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-1fd3f7c8ca994ba290678b3c57babf05
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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