Sodium hydride → HCID 44540141, compound

HRID 1616051Notes

Reaction equation

HRID 1616051 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5][CH2:4]1.[H][H].F[C:13]1[N:18]=[C:17]([C:19]([NH:21][C:22]2[CH:30]=[C:29]([C:31]3[CH:39]=[CH:38][CH:37]=[C:36]4[C:32]=3[CH:33]=[CH:34][NH:35]4)[CH:28]=[C:27]3[C:23]=2[CH:24]=[N:25][NH:26]3)=[O:20])[CH:16]=[CH:15][CH:14]=1>C1COCC1.O>[NH:35]1[C:36]2[C:32](=[C:31]([C:29]3[CH:28]=[C:27]4[C:23]([CH:24]=[N:25][NH:26]4)=[C:22]([NH:21][C:19]([C:17]4[CH:16]=[CH:15][CH:14]=[C:13]([O:9][CH:6]5[CH2:7][CH2:8][O:3][CH2:4][CH2:5]5)[N:18]=4)=[O:20])[CH:30]=3)[CH:39]=[CH:38][CH:37]=2)[CH:33]=[CH:34]1

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 74956Tetrahydro-4H-pyran-4-ol2×HCID 44541051HCID 44541051, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 44540141HCID 44540141, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under an atmosphere of nitrogen, sodium hydride (5 mg, 0.14 mmol, 60% suspension in mineral oil) was added to a solution of tetrahydro-2H-pyran-4-ol (13 mg, 0.14 mmol) in THF (2 ml). After hydrogen evolution was complete, 6-Fluoro-N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-pyridinecarboxamide (50 mg, 0.14 mmol) was added and the mixture was heated to reflux for 1 h. Another portion of tetrahydro-2H-pyran-4-ol (13 mg, 0.14 mmol) and sodium hydride (5 mg, 0.14 mmol) was added and the mixture was heated to reflux overnight. The mixture was cooled to room temperature, water was added and the mixture was extracted with DCM. The organic extracts were combined, dried over MgSO4, filtered and the solvent was removed in vacuo to give an orange oil. This was purified by mass-directed automated preparative HPLC (Method B) to give the title compound (7 mg) as a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 1 h
  3. temperaturethe mixture was heated
  4. temperatureto reflux overnight
  5. extractionthe mixture was extracted with DCM
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customto give an orange oil
  10. customThis was purified

Sources & evidence

ORD record
ord-ca28dd38900342f3a79a24fa9dc28ecb
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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