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

HRID 1943958Notes

Reaction equation

HRID 1943958 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([NH2:12])[CH:10]=2)[NH:5][N:4]=1.[Cl:13][C:14]1[C:22]([NH:23][S:24]([CH2:27][CH2:28][CH3:29])(=[O:26])=[O:25])=[CH:21][CH:20]=[C:19]([Cl:30])[C:15]=1[C:16](O)=[O:17].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.C(OCC)(=O)C>[Cl:13][C:14]1[C:22]([NH:23][S:24]([CH2:27][CH2:28][CH3:29])(=[O:25])=[O:26])=[CH:21][CH:20]=[C:19]([Cl:30])[C:15]=1[C:16]([NH:12][C:9]1[CH:10]=[C:11]2[C:3]([O:2][CH3:1])=[N:4][NH:5][C:6]2=[N:7][CH:8]=1)=[O:17]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 442236943-Methoxy-1H-pyrazolo[3,4-B]pyridin-5-amineHCID 580953672,6-Dichloro-3-(propylsulfonamido)benzoic acid

Product 1

HCID 566822022,6-dichloro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamideYield 35.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3-Methoxy-1H-pyrazolo[3,4-b]pyridin-5-amine (50 mg, 0.305 mmol) in N,N-dimethylformamide (3.0 mL) was sequentially treated with 2,6-dichloro-3-(propylsulfonamido)benzoic acid (356 mg, 1.14 mmol), EDCI (117 mg, 0.609 mmol), and HOBt (82.3 mg, 0.609 mmol) and heated to 60° C. After 72 hours, the reaction mixture was allowed to cool to ambient temperature. The mixture was diluted with ethyl acetate, washed with water (4×), sodium bicarbonate (2×), and brine (1×), dried over sodium sulfate, and concentrated. The crude product was applied directly to a silica gel column and eluted with a gradient (30% to 100%) of ethyl acetate-hexanes to provide 2,6-dichloro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (67.8 mg, 0.0524 mmol, 35.4% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 12.63-12.59 (s, 1H), 11.04-11.00 (s, 1H), 9.83-9.79 (s, 1H), 8.59-8.570 (d, 1H), 8.47-8.45 (d, 1H), 7.60-7.57 (m, 2H), 4.03-4.01 (s, 3H), 3.21-3.13 (m, 2H), 1.83-1.73 (m, 2H), 1.02-0.97 (t, 3H); MS (APCI-neg) m/z=456.1 (M−H).

Workup

  1. temperatureto cool to ambient temperature
  2. washwashed with water (4×), sodium bicarbonate (2×), and brine (1×)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. washeluted with a gradient (30% to 100%) of ethyl acetate-hexanes

Sources & evidence

ORD record
ord-c1ec0da4f90243818931dc767a61aaa5
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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