Diisopropylamine → 6-bromo-2-[2-(2,6-difluoro-3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 1052312Notes

Reaction equation

HRID 1052312 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([O:22][CH3:23])=[C:16]([F:24])[C:15]=1[CH2:25][CH2:26][C:27]1[N:28]=[C:29]2[CH:35]=[CH:34][N:33]([S:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)(=[O:38])=[O:37])[C:30]2=[N:31][CH:32]=1.[Br:45]C(Cl)(Cl)C(Br)(Cl)Cl>O1CCCC1>[Br:45][C:34]1[N:33]([S:36]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)(=[O:38])=[O:37])[C:30]2=[N:31][CH:32]=[C:27]([CH2:26][CH2:25][C:15]3[C:16]([F:24])=[C:17]([O:22][CH3:23])[CH:18]=[C:19]([O:20][CH3:21])[C:14]=3[F:13])[N:28]=[C:29]2[CH:35]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 899629792-[2-(2,6-difluoro-3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazineHCID 178418339Butyllithium

Product 1

HCID 899635876-bromo-2-[2-(2,6-difluoro-3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazineYield 70,456.398%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N,N-diisopropylamine (0.150 mL, 1.07 mmol) in tetrahydrofuran (0.48 mL) at 78° C., n-butyllithium (2.5 M in hexanes, 0.428 mL, 1.07 mmol) was added dropwise. After a white precipitate formed, the mixture was warmed up to 0° C. for 10 minutes. The resulting solution was added to a stirred solution of 2-[2-(2,6-difluoro-3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (400 mg, 0.871 mmol) in tetrahydrofuran (3 mL) at 78° C. After 10 minutes, a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (0.283 g, 0.870 mmol) in tetrahydrofuran (2 mL) was added dropwise. After another 1 hour, the reaction mixture was quenched with saturated aq. NH4Cl, then extracted with methylene chloride. The combined organic layers were dried over MgSO4, then concentrated. The residue was purified on silica gel (eluting with 0 to 50% EtOAc in hexanes) to give the desired product (330 g, 70%). LCMS calculated for C22H19BrF2N3O4S (M+H)+: m/z=538.0. Found: 538.0.

Workup

  1. customAfter a white precipitate formed
  2. waitAfter another 1 hour
  3. customthe reaction mixture was quenched with saturated aq. NH4Cl
  4. extractionextracted with methylene chloride
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (eluting with 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cf60af4adc8643afbb1830e283d3fccc
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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