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

HRID 1943963Notes

Reaction equation

HRID 1943963 reaction equation
[F:1][C:2]1[C:10]([NH:11][S:12](=[O:18])(=[O:17])[NH:13][CH2:14][CH2:15][CH3:16])=[CH:9][CH:8]=[C:7]([F:19])[C:3]=1[C:4]([OH:6])=O.[CH3:20][O:21][C:22]1[C:30]2[C:25](=[N:26][CH:27]=[C:28]([NH2:31])[CH:29]=2)[NH:24][N:23]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[C:10]([NH:11][S:12](=[O:18])(=[O:17])[NH:13][CH2:14][CH2:15][CH3:16])=[CH:9][CH:8]=[C:7]([F:19])[C:3]=1[C:4]([NH:31][C:28]1[CH:29]=[C:30]2[C:22]([O:21][CH3:20])=[N:23][NH:24][C:25]2=[N:26][CH:27]=1)=[O:6]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 442236943-Methoxy-1H-pyrazolo[3,4-B]pyridin-5-amineHCID 670888502,6-difluoro-3-(N-propylsulfamoylamino)benzoic acid

Product 1

HCID 670888762,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(N-propylsulfamoylamino)benzamideYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

2,6-Difluoro-3-(N-propylsulfamoylamino)benzoic acid (0.095 g, 0.32 mmol), 3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-amine (0.053 g, 0.32 mmol), HOBt (0.044 g, 0.32 mmol), and EDCI (0.062 g, 0.32 mmol) were dissolved in DMF (1.6 mL) and stirred at room temperature for 16 hours. The mixture was diluted with EtOAc (30 mL) and washed with a mixture of 1:1:1 water:bicarbonate:brine (3×20 mL). The organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via column chromatography eluting with 1:1 then 8:2 EtOAc:hexanes to provide 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(N-propylsulfamoylamino)benzamide (0.090 g, 0.20 mmol, 63% yield). 1H NMR (400 MHz, CD3OD) δ 8.57-8.60 (m, 1H), 8.47-8.49 (m, 1H), 7.63-7.70 (m, 1H), 7.04-7.11 (m, 1H), 4.07 (s, 3H), 2.94-3.30 (m, 2H), 1.45-1.56 (m, 2H), 0.85-0.90 (m, 3H); m/z (APCI-pos) M+1=441.1.

Workup

  1. washwashed with a mixture of 1:1:1 water
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified via column chromatography
  5. washeluting with 1:1

Sources & evidence

ORD record
ord-e5c71d930629462cacb5c2b6a0b43649
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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