Hydrochloric Acid → 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester

HRID 1931710Notes

Reaction equation

HRID 1931710 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:13][C@@H:14]([OH:17])[CH2:15][CH3:16].N1C=CC=CC=1.Cl.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>ClCCCl.O>[C@H:14]([O:17][C:2]([N:53]1[CH2:52][CH2:51][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:35])=[O:34])=[CH:57][CH:56]=4)=[C:42]3[CH:49]=[N:48]2)[CH2:55][CH2:54]1)=[O:4])([CH2:15][CH3:16])[CH3:13]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 81531DiisopropylethylamineHCID 84682(-)-2-ButanolHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 579648874-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl esterYield 36.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

Triphosgene (217 mg, 0.73 mmol) was added to a solution of (R)-(−)-2-butanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 148 mg, 2 mmol) in a mixture of pyridine (190 μL, 2.3 mmol) and 1,2-dichloroethane (10 mL). The solution was stirred at 40° C. for 3 h and then cooled to room temperature. 1 M aqueous hydrochloric acid (2.5 mL) and water (3 mL) were added. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 220 mg, 0.45 mmol) and diisopropylethylamine (250 μL) were added and the mixture was stirred for 30 min and then chromatographed, eluting with 50-75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester (78 mg, 36%) as an off-white foam/solid.

Workup

  1. temperaturecooled to room temperature
  2. customThe layers were separated
  3. dry with materialthe organic phase was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. stirringthe mixture was stirred for 30 min
  7. customchromatographed
  8. washeluting with 50-75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6176f9f9d84f4f64b679d351adaca44f
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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