1-Hydroxybenzotriazole → 2,6-dichloro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide

HRID 2196735Notes

Reaction equation

HRID 2196735 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.[Cl: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]([Cl:28])[C:13]=1[C:14](O)=[O:15].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[Cl: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]([Cl: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

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 117151871H-pyrrolo(2,3-b)pyridin-5-amineHCID 580953672,6-Dichloro-3-(propylsulfonamido)benzoic acid

Product 1

HCID 566755512,6-dichloro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamideYield 3.41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

1H-Pyrrolo[2,3-b]pyridin-5-amine (192 mg, 1.44 mmol) in N,N-dimethylformamide (7.2 mL) was sequentially treated with 2,6-dichloro-3-(propylsulfonamido)benzoic acid (690.5 mg, 2.212 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (466.4 mg, 2.433 mmol), and 1-hydroxybenzotriazole (328.8 mg, 2.433 mmol) and heated to 60° C. After 24 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-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide (10.5 mg, 0.0246 mmol, 3.41% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 11.70-11.59 (s, 1H), 10.77-10.68 (s, 1H), 9.88-9.75 (s, 1H), 8.39-8.30 (m, 2H), 7.56-7.47 (m, 3H), 6.49-6.45 (d, 1H), 3.21-3.04 (m, 2H), 1.82-1.70 (m, 2H), 1.03-0.95 (t, 3H); MS (APCI-neg) m/z=425.1 (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-a374c2c6a4bc49d4919320f5e36bb4a7
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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