Hydrochloric Acid → HCID 44514686, compound

HRID 1931716Notes

Reaction equation

HRID 1931716 reaction equation
[F:1][C:2]([F:8])([F:7])[C:3]([OH:6])([CH3:5])[CH3:4].Cl[C:10](Cl)([O:12]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.FC(F)(F)C(O)=O.[CH3:29][S:30]([C:33]1[CH:54]=[CH:53][C:36]([O:37][C:38]2[N:43]=[CH:42][N:41]=[C:40]3[N:44]([CH:47]4[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]4)[N:45]=[CH:46][C:39]=23)=[CH:35][CH:34]=1)(=[O:32])=[O:31].C(N(CC)CC)C.[Cl-].[NH4+]>N1C=CC=CC=1.C(OCC)C>[F:1][C:2]([F:8])([F:7])[C:3]([O:6][C:10]([N:50]1[CH2:49][CH2:48][CH:47]([N:44]2[C:40]3=[N:41][CH:42]=[N:43][C:38]([O:37][C:36]4[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:54][CH:53]=4)=[C:39]3[CH:46]=[N:45]2)[CH2:52][CH2:51]1)=[O:12])([CH3:5])[CH3:4]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 681821,1,1-Trifluoro-2-methylpropan-2-olHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 44514686HCID 44514686, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-trifluoromethyl-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 500 mg, 3.91 mmol) in pyridine (347 μL) was added to a cooled (0° C.) solution of triphosgene (386 mg, 1.3 mmol) in diethyl ether (35 mL). The mixture was stirred overnight and then 1 M aqueous hydrochloric acid (4 mL) was added. The organic layer was separated and washed with brine, dried (magnesium sulfate), filtered, and evaporated. The resulting material was dissolved in tetrahydrofuran (5 mL) and the solution was cooled to 0° C. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 210 mg, 0.43 mmol) and triethylamine (560 μL, 4 mmol) were added. The mixture was stirred for 30 min and then poured into saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (magnesium sulfate), filtered, evaporated, and 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-1,1-dimethyl-ethyl ester (20.5 mg, 10%).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe resulting material was dissolved in tetrahydrofuran (5 mL)
  7. stirringThe mixture was stirred for 30 min
  8. extractionextracted three times with ethyl acetate
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried (magnesium sulfate)
  11. filtrationfiltered
  12. customevaporated
  13. custompurified by column chromatography
  14. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-22066c956a4e4dd380f21aece0e86d1b
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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