Hydrochloric Acid → 6-Cyclobutoxy-5-furan-2-yl-nicotinic acid N'-(4-fluoro-phenyl)-hydrazide

HRID 240750Notes

Reaction equation

HRID 240750 reaction equation
[CH:1]1([O:5][C:6]2[C:14]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][N:7]=2)[CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(NC(C)C)(C)C.Cl.[F:50][C:51]1[CH:56]=[CH:55][C:54]([NH:57][NH2:58])=[CH:53][CH:52]=1.Cl>C1COCC1>[F:50][C:51]1[CH:56]=[CH:55][C:54]([NH:57][NH:58][C:10](=[O:12])[C:9]2[CH:13]=[C:14]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)[C:6]([O:5][CH:1]3[CH2:2][CH2:3][CH2:4]3)=[N:7][CH:8]=2)=[CH:53][CH:52]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 699814-Fluorophenylhydrazine hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712944156-Cyclobutoxy-5-furan-2-yl-nicotinic acid

Product 1

HCID 712939596-Cyclobutoxy-5-furan-2-yl-nicotinic acid N'-(4-fluoro-phenyl)-hydrazideYield 62.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 5 mL round-bottomed flask the above prepared 6-cyclobutoxy-5-furan-2-yl-nicotinic acid (0.050 g, 174 μmol, Eq: 1.00) was combined with THF (2 mL) to give a colorless solution. TBTU (83.6 mg, 260 μmol, Eq: 1.5) and N,N-diisopropylamine (112 mg, 152 μL, 868 μmol, Eq: 5) were added. The reaction mixture was stirred for 10 min at RT before (4-fluorophenyl)-hydrazine hydrochloride (33.9 mg, 208 μmol, Eq: 1.2) was added and the reaction allowed to proceed at RT overnight. The mixture was poured into 15 mL 1 M HCl and extracted with EtOAc (2×25 mL). The organic layers were combined, washed with 1 M NaOH, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) to yield 40 mg of the title compound as white solid; MS (EI) 368.4 (M+H)+.

Workup

  1. customto give a colorless solution
  2. additionwas added
  3. extractionextracted with EtOAc (2×25 mL)
  4. washwashed with 1 M NaOH
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-8b6e87edc61d4c51ad9cd9890e26fb2b
Source dataset
uspto-grants-2014_02
Patent number
US08648099B2

Reaction notes

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