p-Toluenesulfonic acid → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde

HRID 1047524Notes

Reaction equation

HRID 1047524 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[Br:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[C:16]2[CH:22]=[O:23].[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C1COCC1.C(Cl)Cl>[Br:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][O:24]1)[N:17]=[C:16]2[CH:22]=[O:23]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 178520023HCID 178520023, compound

Product 1

HCID 866624125-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehydeYield 80%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

p-Toluenesulfonic acid (10 mg, 0.052 mmol) was added to a solution of 5-bromo-indazole-3-carbaldehyde (100 mg, 0.444 mmol) and 3,4-dihydro-2H-pyran (75 mg, 0.891 mmol) in a mixture of THF/CH2Cl2 (1:1, 6 mL). The reaction mixture was stirred for 12 h at room temperature after which the solvent was removed in vacuo. The residue was dissolved in CH2Cl2 (20 mL) and poured in water (20 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (20 mL). The combined organic layers were washed with water (40 mL) and brine (40 mL), dried over Na2SO4 and concentrated. Purification by flash chromatography (CH2Cl2) afforded 110 mg, (80% yield) of the title compound as a solid. 1H NMR (400 MHz, CDCl3): δ 10.21 (s, 1H), 8.47 (s, 1H), 7.56 (m, 2H), 5.80 (dd, 1H, J=3.2 and 9.2 Hz), 3.98 (m, 1H), 3.79-3.74 (m, 1H), 2.57-2.49 (m, 1H), 2.20-2.12 (m, 2H), 1.83-1.57 (m, 3H).

Workup

  1. customwas removed in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (20 mL)
  3. additionpoured in water (20 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (20 mL)
  6. washThe combined organic layers were washed with water (40 mL) and brine (40 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by flash chromatography (CH2Cl2)

Sources & evidence

ORD record
ord-0eea6799732a4d6db69f687c38c15c09
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

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