3,4-dihydro-2H-pyran → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde

HRID 389516Notes

Reaction equation

HRID 389516 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH:11]=[O:12].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][O:13]1)[N:6]=[C:5]2[CH:11]=[O:12]

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 178520023HCID 178520023, compound

Product 1

HCID 866624125-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehydeYield 62.5%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-bromo-1H-indazole-3-carbaldehyde (1.00 g, 4.44 mmol), dihydropyran (912 uL, 10.0 mmol), and p-toluenesulfonic acid monohydrate (16.9 mg, 0.0889 mmol) in DCM (8.8 mL) was stirred at room temperature for 24 h. The reaction was poured into saturated aqueous sodium bicarbonate (10 mL) and extracted with dichloromethane (3×5 mL). The combined organic fractions were washed with saturated aqueous sodium chloride (1×10 mL), dried over sodium sulfate, filtered, and concentrated. Purification by ISCO chromatography (10 to 40% ethyl acetate:heptane) afforded 858 mg (56%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.17 (s, 1 H), 8.28 (d, J=1.8 Hz, 1 H), 7.92 (d, J=8.3 Hz, 1 H), 7.80-7.61 (m, 1 H), 6.08 (dd, J=2.5, 9.3 Hz, 1 H), 3.99-3.69 (m, 2 H), 2.46-2.26 (m, 1 H), 2.17-1.92 (m, 2 H), 1.87-1.67 (m, 1 H), 1.68-1.53 (m, 2 H); MS (ESI): 309.03, 311.05 [M+H]+; HPLC tR=3.38 min (ZQ3, nonpolar—4 min).

Workup

  1. extractionextracted with dichloromethane (3×5 mL)
  2. washThe combined organic fractions were washed with saturated aqueous sodium chloride (1×10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by ISCO chromatography (10 to 40% ethyl acetate:heptane)

Sources & evidence

ORD record
ord-d38725f7346641c2bae1cd208dab0480
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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