Cesium carbonate → 4-chloro-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 527997Notes

Reaction equation

HRID 527997 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1.O1CCCC1.O.[CH3:27][S:28]([N:31]1[CH2:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH2:33][CH2:32]1)(=[O:30])=[O:29].C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C>[Cl:1][C:2]1[C:3]2[CH:10]=[C:9]([C:34]3[CH2:35][CH2:36][N:31]([S:28]([CH3:27])(=[O:30])=[O:29])[CH2:32][CH:33]=3)[N:8]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 21881883Oxolane--water (1/1)HCID 574158854-Chloro-6-iodo-7-phenylsulfonyl-7H-pyrrolo[2,3-D]pyrimidineHCID 679734971-Methanesulfonyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine

Product 1

HCID 904181484-chloro-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-chloro-6-iodo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (1.9 g, 4.53 mmol) in 6:1 tetrahydrofuran/water (60 mL) was added 1-(methylsulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (1.56 g, 5.43 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (0.37 g, 0.453 mmol) and cesium carbonate (3.54 g, 10.87 mmol). The mixture was heated at 50° C. overnight, cooled and diluted with 50 mL ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water, and brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash chromatography on silica (Analogix 280) eluting with a gradient of 10% to 60% ethyl acetate/hexanes gave the title compound. MS (ESI+) m/z 452.5 (M)+.

Workup

  1. temperaturecooled
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water, and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica (Analogix 280)
  7. washeluting with a gradient of 10% to 60% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2dad17fa01554ee489278255ef58a71f
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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