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

HRID 218029

Reaction equation

HRID 218029 reaction equation
[C:1]12([NH2:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][C:3]([NH2:11])([CH2:4]3)[CH2:2]1)[CH2:8]2.CCN(C(C)C)C(C)C.[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([C:28](Cl)=[O:29])=[N:24]1.[S:31]1[CH:35]=[CH:34][N:33]=[C:32]1[C:36](Cl)=[O:37]>C(Cl)Cl>[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([C:28]([NH:12][C:1]23[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][C:3]([NH:11][C:36]([C:32]5[S:31][CH:35]=[CH:34][N:33]=5)=[O:37])([CH2:4]4)[CH2:2]2)[CH2:8]3)=[O:29])=[N:24]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 213512Adamantane-1,3-diamineHCID 27952111,3-Thiazole-2-carbonyl chlorideHCID 128450451-Methyl-1H-pyrazole-3-carbonyl chloride

Product 1

HCID 44633204Thiazole-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amideYield 38.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of adamantane-1,3-diamine (17 mg, 0.1 mmol, Zerenex Molecular Ltd., Greater Manchester, UK) in DCM (2 mL) was added DIEA (20 mg, 0.15 mmol), 1-methyl-1H-pyrazole-3-carbonyl chloride (16 mg, 0.11 mmol; Maybridge Chemical Co., Cornwall, UK) and thiazole-2-carbonyl chloride (16 mg, 0.11 mmol; Maybridge Chemical Co., Cornwall, UK). After stirring at room temperature for 3 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. A shallow gradient between 27-53% of acetonitrile was used between 0.75-3.3 min to separate close-eluting impurities. 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 15 mg (38%) of the title compound, thiazole-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide, as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=3.2 Hz, 1H), 7.53 (d, J=3.2 Hz, 1H), 7.33 (d, J=2.3 Hz, 1H), 7.14 (d, J=2.3 Hz, 1H), 6.74-6.71 (m, 2H), 3.89 (s, 3H), 2.55-2.51 (m, 2H), 2.35-2.29 (m, 2H), 2.19-2.11 (m, 8H), 1.71-1.67 (m, 2H), ESI-MS m/z: 386.0 (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
  6. waitA shallow gradient between 27-53% of acetonitrile was used between 0.75-3.3 min
  7. customto separate
  8. washclose-eluting impurities

Sources & evidence

ORD record
ord-916d88438a0c4c5882ee8ee9d2dd35dc
Source dataset
uspto-grants-2012_06
Patent number
US08198275B2

Linked notes

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