Trifluoroacetic acid → 4-(4-Fluoro-3-trifluoromethyl-benzoylamino)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550825

反応式

HRID 550825 の反応式
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[C:11]2[N:18]=[C:17]([NH:19][C:20]([N:22]3[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]3)=[O:21])[S:16][C:12]=2[N:13]=[CH:14][N:15]=1.[F:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][C:31]=1[C:39]([F:42])([F:41])[F:40].C(N(CC)CC)C>C(Cl)Cl.O>[CH3:8][O:9][C:10]1[C:11]2[N:18]=[C:17]([NH:19][C:20]([N:22]3[CH2:27][CH2:26][CH:25]([NH:28][C:34](=[O:35])[C:33]4[CH:37]=[CH:38][C:30]([F:29])=[C:31]([C:39]([F:42])([F:40])[F:41])[CH:32]=4)[CH2:24][CH2:23]3)=[O:21])[S:16][C:12]=2[N:13]=[CH:14][N:15]=1

参加物

7

反応物 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 590119524-Amino-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

生成物 1

HCID 590119774-(4-Fluoro-3-trifluoromethyl-benzoylamino)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide収率 30.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

A suspension of the trifluoroacetic acid salt of 4-amino-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (prepared as in Example 83, 580 mg, 1.37 mmol), 4-fluoro-3-trifluoromethyl-benzoyl chloride (261 mL, 1.64 mmol) and triethylamine (573 μL, 4.11 mmol) in methylene chloride (15 mL) was stirred at 25° C. overnight. At this time, the reaction was diluted with water and was extracted with ethyl acetate. The organics were washed with a saturated aqueous sodium chloride solution and a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 3:7 ethyl acetate/hexanes to 100% ethyl acetate) afforded 4-(4-fluoro-3-trifluoromethyl-benzoylamino)-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (21 mg, 30.6%) as an off-white solid; ES-HRMS m/e calcd for C20H18F4N6O3S (M+H)+ 499.1170, found 499.1170.

後処理

  1. extractionwas extracted with ethyl acetate
  2. washThe organics were washed with a saturated aqueous sodium chloride solution
  3. dry with materiala saturated aqueous sodium bicarbonate solution, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 3:7 ethyl acetate/hexanes to 100% ethyl acetate)

出典と根拠

ORDレコード
ord-77228ead8fe5416ba38fd0e8a700ed4d
出典データセット
uspto-grants-2011_05
特許番号
US07947692B2

関連ノート

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