Potassium Carbonate → [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile

HRID 500741Notes

Reaction equation

HRID 500741 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[C:10]([C:14]3[CH:15]=[C:16]4[CH:22]=[CH:21][N:20]([S:23]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)(=[O:25])=[O:24])[C:17]4=[N:18][CH:19]=3)=[N:11][NH:12][CH:13]=2)[CH:6]=[CH:5][N:4]=1.Br[CH2:33][C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:26]1([S:23]([N:20]2[C:17]3=[N:18][CH:19]=[C:14]([C:10]4[C:9]([C:7]5[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=5)=[CH:13][N:12]([CH2:33][C:34]#[N:35])[N:11]=4)[CH:15]=[C:16]3[CH:22]=[CH:21]2)(=[O:24])=[O:25])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 1785034265-{4-[2-(methylthio)pyrimidin-4-yl]-1H-pyrazol-3-yl}-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 57856275[3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrileYield 63.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of the 5-{4-[2-(methylthio)pyrimidin-4-yl]-1H-pyrazol-3-yl}-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (C-1-3) (638 mg, 1.42 mmol) and bromoacetonitrile (0.5 mL, 7 mmol) in DMF was added freshly ground Potassium Carbonate (254 mg, 1.84 mmol). The resulting suspension was stirred at 75° C. for 18 hr. LCMS showed complete consumption of starting material. The mixture was partitioned between ethyl acetate and saturated aqueous NaCl. The aqueous layer was extracted with ethyl acetate twice. The combined organics were washed with water twice, saturated aqueous NaCl, dried over MgSO4 and reduced to minimum volume. The residue was purified on silica gel using a gradient of 25 to 100% methyl tert-butyl ether in hexanes as eluent to give [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile (C-1-4) (440 mg, 63%) as a crisp foam. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.46 (d, J=2.02 Hz, 1H), 8.36 (d, J=5.31 Hz, 1H), 8.31 (s, 1H), 8.11-8.16 (m, 2H), 8.09 (d, J=2.02 Hz, 1H), 7.83 (d, J=4.04 Hz, 1H), 7.64-7.71 (m, 1H), 7.57 (t, J=7.71 Hz, 2H), 7.01 (d, J=5.31 Hz, 1H), 6.75 (d, J=4.04 Hz, 1H), 5.26 (s, 2H), 1.88 (s, 3H).

Workup

  1. customconsumption of starting material
  2. customThe mixture was partitioned between ethyl acetate and saturated aqueous NaCl
  3. extractionThe aqueous layer was extracted with ethyl acetate twice
  4. washThe combined organics were washed with water twice
  5. dry with materialsaturated aqueous NaCl, dried over MgSO4
  6. customThe residue was purified on silica gel using a gradient of 25 to 100% methyl tert-butyl ether in hexanes as eluent

Sources & evidence

ORD record
ord-9da970e4d7d54e948dfd80c39f36b9ca
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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