Pyrazole → HCID 68109526, compound

HRID 2179382Notes

Reaction equation

HRID 2179382 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].[Br:8][C:9]1[CH:10]=[C:11]([CH2:29]OS(C)(=O)=O)[C:12]2[O:21][C:20]3[CH2:19][CH2:18][N:17]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:16][C:15]=3[C:13]=2[CH:14]=1>O1CCCC1>[N:1]1([CH2:29][C:11]2[C:12]3[O:21][C:20]4[CH2:19][CH2:18][N:17]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:16][C:15]=4[C:13]=3[CH:14]=[C:9]([Br:8])[CH:10]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 86668000HCID 86668000, compound

Product 1

HCID 68109526HCID 68109526, compoundYield 35.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1H-pyrazole (20 mg, 0.52 mmol) in tetrahydrofuran (3 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 26 mg, 0.39 mmol). After stirring the mixture for 1 h the product of step A (120 mg, 0.26 mmol) was added and the reaction warmed to ambient temperature over 2 h. The reaction mixture was quenched with 5% sodium bicarbonate solution and then extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (95:5 hexanes/ethyl acetate) to give tert-butyl 6-((1H-pyrazol-1-yl)methyl)-8-bromo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (40 mg, 35%) as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 7.55 (d, J=1.5 Hz, 1H), 7.48 (d, J=1.8 Hz, 2H), 7.14 (d, J=1.5 Hz, 1H), 6.28 (t, J=2.1 Hz, 1H), 5.55 (s, 2H), 4.50 (s, 2H), 3.82 (t, J=5.4 Hz, 2H), 2.87 (t, J=5.4 Hz, 2H), 1.50 (s, 9H).

Workup

  1. additionwas added
  2. customThe reaction mixture was quenched with 5% sodium bicarbonate solution
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (95:5 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-0e85901e98ad4b3e801e28ac494ebfc4
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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