Sodium hydride → 2-[6-((1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-yloxy)-indazol-1-yl]-ethanol

HRID 630710Notes

Reaction equation

HRID 630710 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:24]=[C:23]2[C:19]([CH:20]=[N:21][N:22]2[CH2:25][CH2:26][O:27]C2CCCCO2)=[CH:18][CH:17]=1>CN(C=O)C.CCOC(C)=O>[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([O:12][C:16]2[CH:24]=[C:23]3[C:19]([CH:20]=[N:21][N:22]3[CH2:25][CH2:26][OH:27])=[CH:18][CH:17]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866869686-Fluoro-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-indazole

Product 1

HCID 866869692-[6-((1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-yloxy)-indazol-1-yl]-ethanol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Intermediate A (212 mg, 1.3 mmol) was added portionwise to a suspension of sodium hydride (60% in mineral oil, 120 mg, 3.0 mmol) in DMF (3 mL) at RT and stirred for 20 min. A solution of Intermediate 11a (264.3 mg, 1.0 mmol) in DMF (1 mL) was then added dropwise and the resulting mixture stirred at 60° C. for 2.5 h. After cooling, the mixture was diluted with EtOAc (50 mL) and poured onto ice water. The organic layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), filtered and concentrated in vacuo. The residue was loaded on to a SCX-2 cartridge, eluting with MeOH then 2M NH3 in MeOH. Further purification by FCC, using 0-10% [2M NH3 in MeOH] in DCM to give the title compound as a brown oil. LCMS (Method 1): Rt 1.80 min, m/z 323 [MH+].

Workup

  1. stirringthe resulting mixture stirred at 60° C. for 2.5 h
  2. temperatureAfter cooling
  3. additionpoured onto ice water
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washeluting with MeOH
  9. customFurther purification by FCC

Sources & evidence

ORD record
ord-40ba33f57c8142a0b751e981415c6c71
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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