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

HRID 1943965Notes

Reaction equation

HRID 1943965 reaction equation
[Cl:1][C:2]1[C:10]([NH:11][S:12]([CH2:15][CH2:16][CH3:17])(=[O:14])=[O:13])=[CH:9][CH:8]=[C:7]([F:18])[C:3]=1[C:4]([OH:6])=O.[CH3:19][O:20][C:21]1[C:29]2[C:24](=[N:25][CH:26]=[C:27]([NH2:30])[CH:28]=2)[NH:23][N:22]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]([NH:11][S:12]([CH2:15][CH2:16][CH3:17])(=[O:14])=[O:13])=[CH:9][CH:8]=[C:7]([F:18])[C:3]=1[C:4]([NH:30][C:27]1[CH:28]=[C:29]2[C:21]([O:20][CH3:19])=[N:22][NH:23][C:24]2=[N:25][CH:26]=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 580953612-Chloro-6-fluoro-3-(propylsulfonamido)benzoic acid

Product 1

HCID 574006032-chloro-6-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamideYield 15.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Chloro-6-fluoro-3-(propylsulfonamido)benzoic acid (75.7 mg, 0.256 mmol) in N,N-dimethylformamide (2.5 mL) was sequentially treated with 3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-amine (46.2 mg, 0.282 mmol), EDCI (54.0 mg, 0.282 mmol), and HOBt (38.0 mg, 0.282 mmol). The reaction mixture was allowed to stir at ambient temperature for 24 hours. The mixture was then diluted with ethyl acetate and washed with water (4×), sodium bicarbonate (2×), and brine, dried over sodium sulfate and concentrated. The crude product was triturated with DCM to afford 2-chloro-6-fluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (18.0 mg, 0.0407 mmol, 15.9% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 12.62-12.56 (s, 1H), 11.08-11.03 (s, 1H), 9.78-9.65 (s, 1H), 8.61-8.56 (s, 1H), 8.50-8.45 (s, 1H), 7.63-7.55 (m, 1H), 7.44-7.35 (m, 1H), 4.03-3.99 (s, 3H), 3.14-3.07 (m, 2H), 1.83-1.73 (m, 2H), 1.04-0.95 (t, 3H); MS (APCI-neg) m/z=440.1 (M−H).

Workup

  1. washwashed with water (4×), sodium bicarbonate (2×), and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was triturated with DCM

Sources & evidence

ORD record
ord-b019b50d1d3d4b3ba80beb4abba2baff
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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