Diisopropylethylamine → 6-Methyl-pyridine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide

HRID 218030Notes

Reaction equation

HRID 218030 reaction equation
[NH2:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][C:4]([NH:12][C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=4)=[O:14])([CH2:5]3)[CH2:3]1)[CH2:9]2.CCN(C(C)C)C(C)C.[CH3:31][N:32]1[CH:36]=[CH:35][C:34]([C:37](Cl)=[O:38])=[N:33]1>C(Cl)Cl>[CH3:31][N:32]1[CH:36]=[CH:35][C:34]([C:37]([NH:1][C:2]23[CH2:11][CH:6]4[CH2:7][CH:8]([CH2:10][C:4]([NH:12][C:13]([C:15]5[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=5)=[O:14])([CH2:5]4)[CH2:3]2)[CH2:9]3)=[O:38])=[N:33]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 128450451-Methyl-1H-pyrazole-3-carbonyl chlorideHCID 583586056-Methyl-pyridine-2-carboxylic acid (3-amino-adamantan-yl)-amide2×

Product 1

HCID 446332056-Methyl-pyridine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-methyl-pyridine-2-carboxylic acid (3-amino-adamantan-1-yl)-amide (Intermediate 1, 20 mg, 0.07 mmol) in DCM (5 mL) was added DIEA (30 mg, 0.2 mmol) and 1-methyl-1H-pyrazole-3-carbonyl chloride (20 mg, 0.1 mmol, Maybridge Chemical Co., Cornwall, UK). After stirring at room temperature for 16 h, the reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a RP-HPLC/MS purification system (Gradient: acetonitrile in water, 25-95%, in 3.9 minutes with a cycle time of 5 min. Flow rate: 100 mL/min. Mobile phase additive: 25 mM of ammonium formate. Column: Inertsil® C8, 30×50 mm, 5 μm particle size (GL Sciences, Tokyo, Japan)) to afford 10 mg (30%) of the title compound, 6-methyl-pyridine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide, as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.07 (s, br, 1H), 7.95 (d, J=7.7 Hz, 1H), 7.69 (t, J=7.8 Hz, 1H), 7.33 (d, J=2.3 Hz, 1H), 7.26-7.21 (m, 1H), 6.76-6.72 (m, 2H), 3.89 (s, 3H), 2.55 (s, 3H), 2.54-2.52 (m, 2H), 2.35-2.08 (m, 10H), 1.72-1.69 (m, 2H). ESI-MS m/z: 394.1 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on a RP-HPLC/MS purification system (Gradient
  5. waitacetonitrile in water, 25-95%, in 3.9 minutes with a cycle time of 5 min

Sources & evidence

ORD record
ord-dbbb3e7d6f8c4bfc8bf14d91049d7096
Source dataset
uspto-grants-2012_06
Patent number
US08198275B2

Reaction notes

Loading…