3,4-dihydro-2H-pyran → 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529374Notes

Reaction equation

HRID 1529374 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[NH:15][N:14]=[C:13]4[I:19])[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[O:20]1[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][O:20]3)[N:14]=[C:13]4[I:19])[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178506565HCID 178506565, compound

Product 1

HCID 679600395-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1H-indazole (192 mg, 0.53 mmol), 3,4-dihydro-2 h-pyran (96 μL, 1.06 mmol) and p-toluenesulfonic acid monohydrate (20 mg, 0.106 mmol) in THF (3 mL) was heated at reflux overnight (9 h). After cooling to RT, the mixture was concentrated to about 1 mL. The mixture was diluted with EtOAc and saturated NaHCO3 (aq.) and the layers were separated. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-30% EtOAc in hexanes, to provide 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol, 59% yield) as a pale yellow foam. MS (ESI, pos. ion) m/z: 447.0 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight (9 h)
  3. concentrationthe mixture was concentrated to about 1 mL
  4. additionThe mixture was diluted with EtOAc and saturated NaHCO3 (aq.)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was purified by silica gel chromatography
  11. washeluting with a gradient of 0-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-f8f1943f5af04e589308063e4aeeaa59
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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