Pyridine → HCID 57964951, compound

HRID 1931718Notes

Reaction equation

HRID 1931718 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[F:13][C:14]([F:18])([F:17])CO.N1C=CC=CC=1.FC(F)(F)C(O)=O.[CH3:32][S:33]([C:36]1[CH:57]=[CH:56][C:39]([O:40][C:41]2[N:46]=[CH:45][N:44]=[C:43]3[N:47]([CH:50]4[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]4)[N:48]=[CH:49][C:42]=23)=[CH:38][CH:37]=1)(=[O:35])=[O:34].C(N(C(C)C)CC)(C)C>C(Cl)(Cl)(Cl)Cl>[F:18][C:14]([F:13])([F:17])[CH2:7][O:6][C:5]([N:53]1[CH2:54][CH2:55][CH:50]([N:47]2[C:43]3=[N:44][CH:45]=[N:46][C:41]([O:40][C:39]4[CH:38]=[CH:37][C:36]([S:33]([CH3:32])(=[O:34])=[O:35])=[CH:57][CH:56]=4)=[C:42]3[CH:49]=[N:48]2)[CH2:51][CH2:52]1)=[O:11]

Participants

7

Reactant 5

HCID 1049PyridineHCID 64092,2,2-TrifluoroethanolHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 57964951HCID 57964951, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
60 °C

Procedure

Triphosgene (1.6 g, 5.5 mmol) was added to a solution of 2,2,2-trifluoroethanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 500 mg, 5 mmol) in pyridine (6 mmol) and carbon tetrachloride (25 mL). The mixture was heated to 60° C. for 6 h, then cooled and washed with 1 M aqueous hydrochloric acid. The organic layer was dried (magnesium sulfate), filtered, and evaporated carefully using a cold rotary evaporator bath. The resulting material was suspended in dichloromethane (10 mL) and 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 200 mg, 0.41 mmol) and diisopropylethylamine (350 μL, 2 mmol) were added. The mixture was stirred for 15 min and then purified by column chromatography, eluting with 50% ethyl acetate/hexanes, to give 4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-ethyl ester (71 mg, 35%) as a yellow powder.

Workup

  1. temperaturecooled
  2. washwashed with 1 M aqueous hydrochloric acid
  3. dry with materialThe organic layer was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated carefully
  6. custompurified by column chromatography
  7. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6731790878ce4abb9b5215fcfceb6435
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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