Triethylamine → 4-[4-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931618Notes

Reaction equation

HRID 1931618 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH2:9][CH2:8]2)(=[O:4])=[O:3].C(N(CC)CC)C.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([N:34]2[C:38]3=[N:39][CH:40]=[N:41][C:42](Cl)=[C:37]3[CH:36]=[N:35]2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C=O>[C:21]([O:25][C:26]([N:28]1[CH2:29][CH2:30][CH:31]([N:34]2[C:38]3=[N:39][CH:40]=[N:41][C:42]([N:10]4[C:11]5[C:7](=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:13][CH:12]=5)[CH2:8][CH2:9]4)=[C:37]3[CH:36]=[N:35]2)[CH2:32][CH2:33]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27361365-(Methanesulfonyl)-2,3-dihydro-1H-indoleHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Product 1

HCID 579649894-[4-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 21.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

5-(Methylsulfonyl)-indoline (Matrix Scientific, Columbia, S.C., USA; 30 mg, 0.15 mmol) and triethylamine (70 μL, 0.5 mmol) were added to a solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 45 mg, 0.133 mmol) in tetrahydrofuran (1 mL). The mixture was heated to reflux. No reaction had occurred after 2 h. The volatiles were evaporated. Dimethylformamide (1 mL) and cesium carbonate (250 mg, 0.77 mmol) were added. The mixture was heated at 70° C. overnight, then poured into saturated aqueous sodium bicarbonate, and extracted three times with ethyl acetate. The combined organic extracts were washed twice with water and once with brine, dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography eluting with ethyl acetate to give 4-[4-(5-methanesulfonyl-2,3-dihydro-indol-1-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (14 mg, 21%) as an off-white solid.

Workup

  1. temperatureThe mixture was heated to reflux
  2. customThe volatiles were evaporated
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic extracts were washed twice with water and once with brine
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by column chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-9d69c263e0e6430eb99700a055e323df
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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