Sodium hydride → HCID 67092227, compound

HRID 2074097Notes

Reaction equation

HRID 2074097 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[NH:11][N:10]=[C:9]([C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)[CH:8]=2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH:23]1[CH2:26][N:25]([CH:27]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24]1>CN(C=O)C>[C:28]1([CH:27]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:25]2[CH2:26][CH:23]([N:11]3[C:7]([CH2:6][C:5]4[CH:18]=[CH:19][C:2]([F:1])=[CH:3][CH:4]=4)=[CH:8][C:9]([C:12]4[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=4)=[N:10]3)[CH2:24]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 73306101-Benzhydryl-3-iodoazetidineHCID 247947454-{5-[(4-Fluorophenyl)methyl]-1H-pyrazol-3-yl}pyridine

Product 1

HCID 67092227HCID 67092227, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-[5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine (3.7 g, 14.6 mmol) in DMF (40 mL) was added NaH (0.584 g, 14.6 mmol) and the solution was stirred for 10 minutes under nitrogen. 3-Iodo-N-benzhydryl-azetidine (5.61 g, 16.1 mmol) was then added and the reaction mixture was heated to 110° C. for 2 hours under nitrogen. The solvent was removed in-vacuo and the residue was diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O, brine, dried over MgSO4, filtered and stripped to yield a crude mix of regioisomers. The residue was purified by flash chromatography (5:95 MeOH/CH2Cl2) to yield a clean mix of regioisomers that were separated by SF chromatography to yield the title compound as a lyophilized solid (2.35 g, 34%. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 8.62 (d, 2 H), 7.69 (d, 2 H), 7.42 (d, 4 H), 7.24-7.31 (m, 4 H), 7.14-7.24 (m, 2 H), 7.02-7.09 (m, 2 H), 6.97 (s, 2 H), 6.36-6.39 (m, 1 H), 4.74-4.87 (m, 1 H), 4.57 (s, 1 H), 3.94 (s, 2 H), 3.51-3.62 (m, 4 H); m/z (APCI+) for C32H27N4F 475.3 (M+H)+.

Workup

  1. customThe solvent was removed in-vacuo
  2. additionthe residue was diluted with H2O
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with H2O, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customto yield a crude
  8. additionmix of regioisomers
  9. customThe residue was purified by flash chromatography (5:95 MeOH/CH2Cl2)
  10. customto yield
  11. additiona clean mix of regioisomers that
  12. customwere separated by SF chromatography

Sources & evidence

ORD record
ord-6c65a4e675804e94832d92d57626c8c9
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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