Sodium hydride → HCID 86687165, compound

HRID 2285163Notes

Reaction equation

HRID 2285163 reaction equation
[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([O:14][C:16]2[CH:17]=[CH:18][C:19]3[N:20]([C:22]([N:25]([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:27])[CH3:28])=[N:23][N:24]=3)[CH:21]=2)[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687166HCID 86687166, compound

Product 1

HCID 86687165HCID 86687165, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (60% in mineral oil, 136 mg, 3.39 mmol) in DMF (5 mL) was added Intermediate A (138 mg, 0.85 mmol) and the reaction mixture was stirred for 15 min at RT. A solution of Intermediate 103b (200 mg, 0.85 mmol) in DMF (3 mL) was added and the reaction mixture was heated at 60° C. for 1 h. The reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (220 mg, 68%). LCMS (Method 4): Rt 2.07 min, m/z 380 [MH+].

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for 1 h
  2. customThe reaction mixture was quenched by careful addition of MeOH
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 2M NH3 in MeOH
  5. additionThe product containing fractions
  6. concentrationwere concentrated in vacuo
  7. customthe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-500d506b2a2b4813a518de11dfe2bd3d
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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