2-Aminoadamantane → 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide

HRID 12865

Reaction equation

HRID 12865 reaction equation
[C:1]([N:5]1[C:9]([C:10]([F:13])([F:12])[F:11])=[C:8]([C:14]([OH:16])=O)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[B-](F)(F)(F)F.CN(C(O[N:39]1[C:44](=O)[CH2:43][CH2:42][C:40]1=[O:41])=[N+](C)C)C.[CH:46]12[CH2:55]C3CC(C[CH:48]([CH2:49]3)[CH:47]1N)[CH2:53]2>CN(C)C=O.C(Cl)Cl>[OH:41][C:40]12[CH2:49][CH:48]3[CH2:47][CH:46]([CH2:55][CH:43]([CH:44]3[NH:39][C:14]([C:8]3[CH:7]=[N:6][N:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:9]=3[C:10]([F:11])([F:12])[F:13])=[O:16])[CH2:42]1)[CH2:53]2

Participants

6

Reactant 4

HCID 253322-AminoadamantaneHCID 81531DiisopropylethylamineHCID 14820391-tert-Butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acidHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate

Product 1

HCID 589728631-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amideYield 32.3%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2.334 g; 9.88 mmol) in N,N-dimethylformamide/methylene chloride (1:4 ratio, 15 mL) at room temperature was added diisopropylethylamine (9.00 mL; 51.13 mmol). TSTU (5.420 g; 18.0 mmol) was then added. The resulting mixture was allowed to stir at room temperature for 2 hr and then 2-adamantylamine (1.654 g; 9.89 mmol) was added. The mixture was allowed to stir over night at room temperature and then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed sequentially with 0.5N HCl, saturated sodium bicarbonate then brine, dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product as a light brown solid. Purification by column chromatography (RediSep-120 g silica gel, 10%—100% ethyl acetate/hexanes) provided the desired trans-isomer of 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide (1.23 g, 32%) as a white solid. by resulting light yellow gum was triturated with diethyl ether to provide 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (4.02 g, 80%) as a white powder. The cis-isomer was also isolated (1.58 g, 41%).

Workup

  1. stirringto stir over night at room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. washThe organic layer was washed sequentially with 0.5N HCl, saturated sodium bicarbonate
  5. dry with materialbrine, dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product as a light brown solid
  9. customPurification by column chromatography (RediSep-120 g silica gel, 10%—100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5cb9de90ff894ef8a2ca2cb857c828c3
Source dataset
uspto-grants-2010_06
Patent number
US07728029B2

Linked notes

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