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

HRID 1942239Notes

Reaction equation

HRID 1942239 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-61c4fe2d02f046bcabbec37a0ea3eecc
Source dataset
uspto-grants-2013_03
Patent number
US08389519B2

Reaction notes

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