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

HRID 68921Notes

Reaction equation

HRID 68921 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[I:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[N:12]=[C:11]2[C:23](N(OC)C)=[O:24]>C1COCC1>[I:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[N:12]=[C:11]2[CH:23]=[O:24]

Participants

4

Reactant 2

HCID 205807395-iodo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 205807365-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehydeYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (160 mg, 4.21 mmol) was added in portions to a cooled (0° C.) solution of 5-iodo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide (XI) (1.46 g, 3.5 mmol) in THF. Stirring was continued at 0° C. until the reaction was completed, approximately 30 min. The reaction was quenched by the slow addition of EtOAc at 0° C., and the whole mixture was poured into 0.4 N NaHSO4. The organic layer was washed with brine, dried over MgSO4, concentrated, and purified on a silica gel column (100% EtOAc→3:97 MeOH:DCM) to give 5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (I) as a white solid (0.90 g, 3.15 mmol, 72% yield). 1H NMR (DMSO-d6) δ ppm 1.50-1.71 (m, 2H), 1.71-1.87 (m, 1H), 1.97-2.15 (m, 2H), 2.31-2.42 (m, 1H), 3.66-3.99 (m, 2H), 5.96-6.17 (m, 1H), 7.78 (d, J=6 Hz, 1H), 7.84 (d, J=6 Hz, 1H), 8.50 (s, 1H), 10.13 (s, 1H); ESIMS found for C13H13IN2O2 m/z 357 (M+H).

Workup

  1. customwas continued at 0° C. until the reaction
  2. customThe reaction was quenched by the slow addition of EtOAc at 0° C.
  3. additionthe whole mixture was poured into 0.4 N NaHSO4
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. custompurified on a silica gel column (100% EtOAc→3:97 MeOH:DCM)

Sources & evidence

ORD record
ord-2ae682f4972244d4be757cbc00b79354
Source dataset
uspto-grants-2014_09
Patent number
US08822478B2

Reaction notes

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