Dimethylformamide → HCID 44223229, compound

HRID 2196657Notes

Reaction equation

HRID 2196657 reaction equation
[F:1][C:2]1[C:29]([NH:30][S:31]([CH2:34][CH2:35][CH3:36])(=[O:33])=[O:32])=[CH:28][CH:27]=[C:26]([F:37])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:15](I)=[CH:14][N:13](S(C3C=CC=CC=3)(=O)=O)[C:10]2=[N:11][CH:12]=1)=[O:5].C([O-])([O-])=O.[K+].[K+].[CH3:44][N:45](C=O)C>CO.O>[C:44]([C:15]1[C:9]2[C:10](=[N:11][CH:12]=[C:7]([NH:6][C:4](=[O:5])[C:3]3[C:26]([F:37])=[CH:27][CH:28]=[C:29]([NH:30][S:31]([CH2:34][CH2:35][CH3:36])(=[O:32])=[O:33])[C:2]=3[F:1])[CH:8]=2)[NH:13][CH:14]=1)#[N:45]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 67155879HCID 67155879, compound

Product 1

HCID 44223229HCID 44223229, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

2,6-Difluoro-N-(3-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (0.025 g, 0.0379 mmol) and Cu(I)CN (0.0678 g, 0.758 mmol) were taken up in DMF (0.5 mL) and heated to 100° C. overnight. The solution was partitioned between water and EtOAc. The organic portion was washed with water (3×), brine, dried over Na2SO4 and concentrated to an oil, N-(3-cyano-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide. The oil (0.021 g, 0.038 mmol) was dissolved in MeOH (1.0 mL) and water (0.3 mL). K2CO3 (0.053 g, 0.38 mmol) was added, and the mixture stirred for 1 hour at room temperature. The solution was partitioned between water and EtOAc. The organic layer was washed with water (3×), brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (5% MeOH/DCM) giving N-(3-cyano-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (2.9 mg, 18%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.57-8.58 (m, 1H), 8.52-8.53 (m, 1H), 8.47 (s, 1H), 7.53-7.59 (m, 1H), 7.25-7.29 (m, 1H), 3.09-3.13 (m, 2H), 1.74-1.80 (m, 2H), 0.98-1.01 (m, 3H); m/z (APCI-neg) M−1=418.2.

Workup

  1. customThe solution was partitioned between water and EtOAc
  2. washThe organic portion was washed with water (3×), brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to an oil, N-(3-cyano-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide
  5. customThe solution was partitioned between water and EtOAc
  6. washThe organic layer was washed with water (3×), brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (5% MeOH/DCM)

Sources & evidence

ORD record
ord-3cd811e0bd264c95aae34378d8ec1022
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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