Picolinic acid → Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide

HRID 218022

Reaction equation

HRID 218022 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:41][C:42]12[CH2:51][CH:46]3[CH2:47][CH:48]([CH2:50][C:44]([OH:52])([CH2:45]3)[CH2:43]1)[CH2:49]2>CN(C=O)C>[OH:52][C:44]12[CH2:50][CH:48]3[CH2:47][CH:46]([CH2:51][C:42]([NH:41][C:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[O:9])([CH2:49]3)[CH2:43]1)[CH2:45]2

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 8471TriethylamineHCID 6586453-Amino-1-adamantanolHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59161068Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amideYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 40 ml vial was added picolinic acid (0.68 g, 5.5 mmol), DMF (15 ml), triethylamine (0.90 mL, 6.4 mmol), and O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 2.3 g, 6.0 mmol). The mixture was stirred at rt for 5 minutes to get a clear solution. 3-Amino-adamantanol (0.84 g, 5.0 mmol; AK Scientific, 897-4G Independence Ave., Mountain View, Calif. 94043) was added to the above solution and stirred at rt for 2 hours. DMF was removed in Genevac and the residue was dissolved in DCM (20 mL), washed with 1N aqueous NaOH, water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 1.32 g (97%) of crude title compound, pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide, as an oil, which became a colorless solid upon standing at room temperature. LC/MS (Gradient: acetonitrile in water, 20-85%, in 1.7 minutes with a cycle time of 2 min. Flow rate: 5.0 mL/min. Mobile phase additive: 30 mM of ammonium formate. Column: Inertsil® ODS-3, 50×4.6 mm, 3 μm particle size (GL Sciences, Tokyo, Japan)): Retention time: 0.79 min; purity (UV254): 100%; ESI-MS m/z: 273 (M+H)+. It was used in the next step without further purification.

Workup

  1. customto get a clear solution
  2. stirringstirred at rt for 2 hours
  3. customDMF was removed in Genevac
  4. dissolutionthe residue was dissolved in DCM (20 mL)
  5. washwashed with 1N aqueous NaOH, water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7edd756cefe4ed9ae60ac6daff93c1d
Source dataset
uspto-grants-2012_06
Patent number
US08198275B2

Linked notes

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