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

HRID 12865

反応式

HRID 12865 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 22350042dichloromethane N,N-dimethylformamide溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-5cb9de90ff894ef8a2ca2cb857c828c3
出典データセット
uspto-grants-2010_06
特許番号
US07728029B2

関連ノート

読み込み中…