Hydrochloric Acid → 5-(4-Cyano-phenyl)-N-(4-hydroxy-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

HRID 240742Notes

Reaction equation

HRID 240742 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:11][CH:12]=[C:13]([CH:17]=2)[C:14]([OH:16])=O)=[CH:5][CH:4]=1)#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:55][N:56]1[CH2:61][CH2:60][CH:59]([OH:62])[CH2:58][CH2:57]1.Cl>CCOC(C)=O.CN(C=O)C.C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([O:18][CH2:19][C:20]([F:22])([F:23])[F:21])=[N:11][CH:12]=[C:13]([CH:17]=2)[C:14]([NH:55][N:56]2[CH2:61][CH2:60][CH:59]([OH:62])[CH2:58][CH2:57]2)=[O:16])=[CH:5][CH:4]=1)#[N:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 121256451-Aminopiperidin-4-OLHCID 666787005-(4-Cyanophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

Product 1

HCID 712939835-(4-Cyano-phenyl)-N-(4-hydroxy-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 5 mL round-bottomed flask, the above prepared 5-(4-cyano-phenyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (0.050 g, 155 μmol, Eq: 1.00) was combined with THF (1 mL) and DMF (1 mL) to give a colorless solution. TBTU (74.7 mg, 233 μmol, Eq: 1.5) and N,N-diisopropyl-ethylamine (100 mg, 135 μL, 776 μmol, Eq: 5) were added. The reaction mixture was stirred for 10 min at RT, then 1-aminopiperidin-4-ol (21.6 mg, 186 μmol, Eq: 1.2, CAN 79414-82-7) was added and the reaction mixture kept at RT overnight. Pouring into 25 mL 1 M HCl, extraction with EtOAc (2×50 mL), washing with 1 M NaOH, drying over Na2SO4 and evaporation of all solvents in vacuo, followed by stirring for 15 min with 3 mL of heptane containing 3 drops of EtOAc, generated 51 mg of the title compound as white solid; MS (EI) 421.1 (M+H)+.

Workup

  1. customto give a colorless solution
  2. waitthe reaction mixture kept at RT overnight
  3. washwashing with 1 M NaOH
  4. dry with materialdrying over Na2SO4 and evaporation of all solvents in vacuo
  5. stirringby stirring for 15 min with 3 mL of heptane containing 3 drops of EtOAc

Sources & evidence

ORD record
ord-c8360572b7914669bfa75517d570e585
Source dataset
uspto-grants-2014_02
Patent number
US08648099B2

Reaction notes

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