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

HRID 550825Notes

Reaction equation

HRID 550825 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-77228ead8fe5416ba38fd0e8a700ed4d
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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