N,N,N',N'-Tetramethylethylenediamine → HCID 68234621, compound

HRID 2276756Notes

Reaction equation

HRID 2276756 reaction equation
CS(Cl)(=O)=O.[C:6]([O:10][C:11](=[O:33])[N:12]([CH2:22][C:23]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)([CH3:25])[CH3:24])[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20]O)=[CH:15][N:14]=1)([CH3:9])([CH3:8])[CH3:7].C[N:35](CCN(C)C)C.[N-]=[N+]=[N-].[Na+]>C(OCC)(=O)C.O>[NH2:35][CH2:20][CH2:19][C:16]1[CH:17]=[CH:18][C:13]([N:12]([CH2:22][C:23]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)([CH3:24])[CH3:25])[C:11](=[O:33])[O:10][C:6]([CH3:9])([CH3:7])[CH3:8])=[N:14][CH:15]=1

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 68234528HCID 68234528, compound

Product 1

HCID 68234621HCID 68234621, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Methanesulfonyl chloride (87 μL, 1.1 mmol, 1.1 equiv) dissolved in 2 mL ethyl acetate was added to a 20 dram vial. To this stirring mixture was added a mixture of tert-butyl-2-(4-fluorophenyl)-2-methylpropyl(5-(2-hydroxyethyl)pyridin-2-yl)-carbamate (414 mg, 1.1 mmol, 1.0 equiv), TMEDA (167 μL, 1.1 mmol, 1.1 equiv), and ethyl acetate (3 mL) in a dropwise manner. The reaction was stirred for 1 h. The reaction mixture was then filtered and washed with saturated sodium bicarbonate and brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The resultant solid was dissolved in DMF (4 mL), followed by the addition of sodium azide (139 mg, 2.1 mmol, 2.0 equiv). The reaction was stirred for 24 h, then diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The crude solid was dissolved in methanol, followed by the addition of 10% palladium on carbon (80 mg), potassium carbonate (100 mg). The reaction was stirred under 45 psi of hydrogen for 24 h, filtered, and concentrated to give tert-butyl 5-(2-aminoethyl)pyridin-2-yl(2-(4-fluorophenyl)-2-methylpropyl)carbamate.

Workup

  1. additionwas added to a 20 dram vial
  2. additionTo this stirring mixture was added
  3. filtrationThe reaction mixture was then filtered
  4. washwashed with saturated sodium bicarbonate and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe resultant solid was dissolved in DMF (4 mL)
  9. stirringThe reaction was stirred for 24 h
  10. extractionextracted with ethyl acetate (20 mL)
  11. dry with materialThe organic layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe crude solid was dissolved in methanol
  15. additionfollowed by the addition of 10% palladium on carbon (80 mg), potassium carbonate (100 mg)
  16. stirringThe reaction was stirred under 45 psi of hydrogen for 24 h
  17. filtrationfiltered
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-7de5f192e19d41da8e0e850f74bc6833
Source dataset
uspto-grants-2015_09
Patent number
US09133123B2

Reaction notes

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