Diisopropylethylamine → 5-Cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid N'-(4-fluoro-phenyl)-N'-methyl-hydrazide

HRID 240737Notes

Reaction equation

HRID 240737 reaction equation
[CH:1]1([C:4]2[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[N:6][CH:7]=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[F:51][C:52]1[CH:57]=[CH:56][C:55]([N:58]([CH3:60])[NH2:59])=[CH:54][CH:53]=1>CN(C=O)C.O1CCCC1>[F:51][C:52]1[CH:57]=[CH:56][C:55]([N:58]([CH3:60])[NH:59][C:9](=[O:11])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[N:6][CH:7]=2)=[CH:54][CH:53]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712941085-Cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinic acidHCID 866781051-(4-Fluorophenyl)-1-methylhydrazine hydrochloride

Product 1

HCID 712940105-Cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid N'-(4-fluoro-phenyl)-N'-methyl-hydrazide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 10 mL two-necked flask, the above synthesized 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinic acid (50 mg, 191 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.00 ml) and DMF (1 ml) to give a colorless solution. TBTU (92.2 mg, 287 μmol, Eq: 1.5) and N,N-diisopropylethylamine (124 mg, 167 μl, 957 μmol, Eq: 5) were added and the reaction mixture was stirred for 10 min at rt; then 1-(4-fluorophenyl)-1-methylhydrazine hydrochloride (40.6 mg, 230 μmol, Eq: 1.2; CAN 1978-54-7) was added and the reaction allowed to proceed over night at rt. The reaction mixture was then quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl solution. The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered finally 70 mg of the title product as white semisolid; MS (EI) 384.3 (M+H)+.

Workup

  1. customto give a colorless solution
  2. waitto proceed over night at rt
  3. customThe reaction mixture was then quenched with 1 M HCl (10 mL)
  4. extractionextracted with EtOAc (2×20 mL)
  5. washThe organic layers were washed with 1 M NaOH
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-44ead63d25474bbd9599539b9b218bf0
Source dataset
uspto-grants-2014_02
Patent number
US08648099B2

Reaction notes

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