Sodium hydride → HCID 86686698, compound

HRID 572090Notes

Reaction equation

HRID 572090 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C@H:5]([OH:13])[CH2:4][CH2:3]1.[H-].[Na+].F[C:17]1[CH:18]=[CH:19][C:20]2[N:21]([C:23]([CH:26]([CH3:28])[CH3:27])=[N:24][N:25]=2)[CH:22]=1>CN(C=O)C>[F:12][C:9]1[CH:10]=[C:11]2[C:6]([C@H:5]([O:13][C:17]3[CH:18]=[CH:19][C:20]4[N:21]([C:23]([CH:26]([CH3:28])[CH3:27])=[N:24][N:25]=4)[CH:22]=3)[CH2:4][CH2:3][C@@H:2]2[NH2:1])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 587839636-Fluoro-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridineHCID 86686696(1R,4S)-4-Amino-6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-ol

Product 1

HCID 86686698HCID 86686698, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Intermediate 19a (837 mg, 4.62 mmol) was dissolved in dry DMF (15 mL) under Ar, then NaH (60% in mineral oil, 556 mg, 13.9 mmol) was added, and the mixture stirred for 15 min. Intermediate 1f (893 mg, 4.99 mmol) was added, and the reaction heated at 60° C. for 2 h. The reaction was cooled, quenched by addition of water and extracted with DCM (4×30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by FCC, eluting with 0-20% [2M NH3 in MeOH] in DCM, to give the title compound (429 mg, 27%). LCMS (Method 3): Rt 1.96, m/z 363 [MNa+].

Workup

  1. temperatureThe reaction was cooled
  2. customquenched by addition of water
  3. extractionextracted with DCM (4×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by FCC
  9. washeluting with 0-20% [2M NH3 in MeOH] in DCM

Sources & evidence

ORD record
ord-b774827af4f24bbba87431136ebdeb53
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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