1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide

HRID 2196645Notes

Reaction equation

HRID 2196645 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH2:10])[CH:9]=[C:4]2[CH:3]=[CH:2]1.[F:11][C:12]1[C:20]([NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:24])=[O:23])=[CH:19][CH:18]=[C:17]([F:28])[C:13]=1[C:14](O)=[O:15].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:11][C:12]1[C:20]([NH:21][S:22]([CH2:25][CH2:26][CH3:27])(=[O:23])=[O:24])=[CH:19][CH:18]=[C:17]([F:28])[C:13]=1[C:14]([NH:10][C:8]1[CH:9]=[C:4]2[CH:3]=[CH:2][NH:1][C:5]2=[N:6][CH:7]=1)=[O:15]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 117151871H-pyrrolo(2,3-b)pyridin-5-amineHCID 461929232,6-Difluoro-3-[(propylsulfonyl)amino]benzoic acid

Product 1

HCID 441994082,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamideYield 52.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1H-Pyrrolo[2,3-b]pyridin-5-amine (9.97 g, 74.88 mmol), 2,6-difluoro-3-(propylsulfonamido)benzoic acid (23.00 g, 82.37 mmol), EDCI (15.79 g, 82.37 mmol), and HOBt (11.13 g, 82.37 mmol) were charged to a 2 L round-bottomed flask. DMF was added to give a homogeneous solution, and the reaction mixture was stirred at room temperature overnight. The solution was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with water (3×), brine, dried over Na2SO4 and concentrated to a slurry. DCM (500 mL) was added to this slurry, and the mixture was reconcentrated. Additional DCM (500 mL) was added, and the slurry was filtered, washed with DCM and dried under vacuum providing 2,6-difluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide (15.49 g, 52.5%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 11.65 (br s, 1H), 10.85 (s, 1H), 9.79 (br s, 1H), 8.34-8.37 (m, 2H), 7.51-7.57 (m, 1H), 7.48-7.50 (m, 1H), 6.46-6.48 (m, 1H), 3.11-3.15 (m, 2H), 1.75-1.80 (m, 2H), 0.98-1.02 (m, 3H); m/z (APCI-pos) M+1=395.1.

Workup

  1. customto give a homogeneous solution
  2. customThe solution was partitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washthe combined organics were washed with water (3×), brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a slurry
  7. additionDCM (500 mL) was added to this slurry
  8. additionAdditional DCM (500 mL) was added
  9. filtrationthe slurry was filtered
  10. washwashed with DCM
  11. customdried under vacuum

Sources & evidence

ORD record
ord-acb623309de249999ce4081c269e3837
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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