Ethanol → Pyridine-2-carboxylic acid (3-amino-adamantan-1-yl)-amide

HRID 550866Notes

Reaction equation

HRID 550866 reaction equation
ClCC([NH:5][C:6]12[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][C:8]([NH:16][C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)=[O:18])([CH2:9]3)[CH2:7]1)[CH2:13]2)=O.NC(N)=S.C(O)C.[OH-].[Na+]>O.C(O)(=O)C>[NH2:5][C:6]12[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][C:8]([NH:16][C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)=[O:18])([CH2:9]3)[CH2:7]1)[CH2:13]2

Participants

7

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 2723790ThioureaHCID 59161099Pyridine-2-carboxylic acid [3-(2-chloro-acetylamino)-adamantan-1-yl]amide

Product 1

HCID 58358509Pyridine-2-carboxylic acid (3-amino-adamantan-1-yl)-amideYield 102.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
78 °C

Procedure

To a 40 ml vial containing pyridine-2-carboxylic acid [3-(2-chloro-acetylamino)adamantan-1-yl]-amide (1.69 g, 4.85 mmol, from step 2) and thiourea (0.56 g, 7.4 mmol), was added ethanol (20.0 mL), and acetic acid (4.0 mL). The mixture was stirred at 78° C. overnight. The reaction solution was cooled to rt, poured into water (100 mL), and the pH of the solution was adjusted to 10-13 using 10 N aq. NaOH. The mixture was transferred into a separation funnel, extracted with DCM (3×150 mL). Combined organic layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 1.35 g (95.4%) of crude title compound, pyridine-2-carboxylic acid (3-amino-adarnantan-1-yl)-amide, as an oil, which became a colorless solid upon standing at room temperature. LC-MS (Gradient: acetonitrile in water, 10-85%, 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® C8, 50×4.6 mm, 3 μm particle size (GL Sciences, Tokyo, Japan)): Retention time: 0.63 min; purity (UV254 ): 93%; ESI-MS m/z: 272 (M+H)+. It was used in the next step, amidation, without further purification.

Workup

  1. temperatureThe reaction solution was cooled to rt
  2. customThe mixture was transferred into a separation funnel
  3. extractionextracted with DCM (3×150 mL)
  4. washCombined organic layer was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fd93061a8b7f4ddaaac25e0f5bf08f26
Source dataset
uspto-grants-2011_05
Patent number
US07947680B2

Reaction notes

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