3,4-dihydro-2H-pyran → 5-iodo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide

HRID 889128Notes

Reaction equation

HRID 889128 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([N:13]([O:15][CH3:16])[CH3:14])=[O:12].[O:17]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:18]1[CH2:19][CH2:20][CH2:21][CH2:22][O:17]1)[N:6]=[C:5]2[C:11]([N:13]([O:15][CH3:16])[CH3:14])=[O:12]

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 205807385-iodo-N-methoxy-N-methyl-1H-indazole-3-carboxamide

Product 1

HCID 205807395-iodo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamideYield 92%

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-iodo-N-methoxy-N-methyl-1H-indazole-3-carboxamide (X) (16.5 g, 50 mmol), 3,4-dihydro-2H-pyran (10.3 mL, 113 mmol) and PPTS (0.12 g, 0.6 mmol) in DCM was heated to reflux for 5 hours. The solution was poured into a saturated NaHCO3 solution, the layers were separated, and the aqueous layer was extracted with DCM. The combined organic layers were washed with 5% aqueous citric acid and brine, dried over MgSO4, and concentrated. The crude product was purified on a silica gel column (100% EtOAc→3:97 MeOH:DCM) to provide 5-iodo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide (XI) as a white viscous oil (19.1 g, 46 mmol, 92% yield). 1H NMR (DMSO-d6) δ ppm 1.28-1.84 (m, 6H), 3.43 (s, 3H), 3.60-4.04 (s, 5H), 5.86-6.08 (m, 1H), 7.45-7.87 (m, 2H), 8.39 (s, 1H); ESIMS found for C15H18IN3O3 m/z 416 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 hours
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted with DCM
  5. washThe combined organic layers were washed with 5% aqueous citric acid and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified on a silica gel column (100% EtOAc→3:97 MeOH:DCM)

Sources & evidence

ORD record
ord-3c2abc31e6764329b1acaca415473cda
Source dataset
uspto-grants-2012_08
Patent number
US08252812B2

Reaction notes

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