1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,6-difluoro-N-(3-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide

HRID 1943939Notes

Reaction equation

HRID 1943939 reaction equation
[F:1][CH2:2][CH2:3][O:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([NH2:14])[CH:12]=2)[NH:7][N:6]=1.[F:15][C:16]1[C:24]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])=[CH:23][CH:22]=[C:21]([F:32])[C:17]=1[C:18](O)=[O:19].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[F:15][C:16]1[C:24]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:27])=[O:28])=[CH:23][CH:22]=[C:21]([F:32])[C:17]=1[C:18]([NH:14][C:11]1[CH:12]=[C:13]2[C:5]([O:4][CH2:3][CH2:2][F:1])=[N:6][NH:7][C:8]2=[N:9][CH:10]=1)=[O:19]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 442237483-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-amineHCID 461929232,6-Difluoro-3-[(propylsulfonyl)amino]benzoic acid

Product 1

HCID 866525062,6-difluoro-N-(3-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-amine (0.020 g, 0.10 mmol), 2,6-difluoro-3-(propylsulfonamido)benzoic acid (0.031 g, 0.11 mmol), EDCI (0.021 g, 0.11 mmol), and HOBt (0.017 g, 0.11 mmol) in DMF (6 mL) was stirred at room temperature for 1 hour. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give 2,6-difluoro-N-(3-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide. The crude material was purified by silica gel flash column chromatography (5% 7N NH3-MeOH in CH2Cl2) to afford 2,6-difluoro-N-(3-(2-fluoroethoxy)-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (41 mg, 88% yield). LRMS (ACPI pos) m/e 458.1 (M+1). 1H-NMR (400 MHz, d6-DMSO) δ 12.68 (s, 1H), 11.12 (s, 1H), 9.73 (br s, 1H), 8.58 (d, 1H), 8.54 (d, 1H), 7.55 (q, 1H), 7.27 (t, 1H), 4.90 (m, 1H), 4.78 (m, 1H), 4.63 (m, 1H), 4.55 (m, 1H), 3.12 (t, 2H), 1.76 (m, 2H), 0.99 (t, 3H); 19F NMR (376 MHz, DMSO) δ−117.3, −122.6, −223.1.

Workup

  1. washwashed with saturated aqueous NH4Cl, saturated aqueous NaHCO3 and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-107cf8fa4c9142caaee3fc136cff0389
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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