3-Aminopyridine → 5-Cyclohex-1-enyl-N-ethyl-N-isopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

HRID 469770Notes

Reaction equation

HRID 469770 reaction equation
[C:1]1([C:7]2[C:8]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:9][CH:10]=[C:11]([CH:15]=2)[C:12]([OH:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.NC1C=NC=CC=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:51]([N:54](CC)[CH:55](C)[CH3:56])([CH3:53])[CH3:52]>CN(C=O)C>[C:1]1([C:7]2[C:8]([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[N:9][CH:10]=[C:11]([CH:15]=2)[C:12]([N:54]([CH2:55][CH3:56])[CH:51]([CH3:53])[CH3:52])=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 4

HCID 100093-AminopyridineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712941075-Cyclohex-1-enyl-6-(2,2,2-trifluoroethoxy)nicotinic acid

Product 1

HCID 712943525-Cyclohex-1-enyl-N-ethyl-N-isopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Cyclohex-1-enyl-6-(2,2,2-trifluoroethoxy)nicotinic acid (15 mg, 49.8 μmol) was dissolved in DMF (5 mL) to give a light yellow solution. 3-Amino-pyridine (5.15 mg, 54.8 mmol), TBTU (24.0 mg, 74.7 μmol) and N,N-diisopropylethylamine (32.2 mg, 43.5 μA, 249 μmol) was successively added under stirring and argon to give a light brown solution. The reaction mixture was stirred for 18 h; poured into 5 mL 1N NaOH/ice water and extracted with i-propyl acetate (2×20 mL). The organic layers were combined, washed with brine (1×10 mL), dried with Na2SO4 and concentrated in vacuo to give a brown oil. The crude material was purified by preparative TLC (silica gel, 1.0 mm, n-heptane/i-propyl acetate 1:1) to give the title compound as side product (5 mg, 27%) in form of a colorless oil; LC-MS (UV peak area/ESI) 94%, 371.1936 (M+H)+.

Workup

  1. customto give a light yellow solution
  2. customargon to give a light brown solution
  3. stirringThe reaction mixture was stirred for 18 h
  4. extractionextracted with i-propyl acetate (2×20 mL)
  5. washwashed with brine (1×10 mL)
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. customThe crude material was purified by preparative TLC (silica gel, 1.0 mm, n-heptane/i-propyl acetate 1:1)

Sources & evidence

ORD record
ord-b7ebf89a93774f22aae2889be96a4b4d
Source dataset
uspto-grants-2014_01
Patent number
US08629166B2

Reaction notes

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