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

HRID 2196734Notes

Reaction equation

HRID 2196734 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]([F: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]([F: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 580953612-Chloro-6-fluoro-3-(propylsulfonamido)benzoic acid

Product 1

HCID 442239162-chloro-6-fluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamideYield 25.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1H-Pyrrolo[2,3-b]pyridin-5-amine (20 mg, 0.150 mmol) in N,N-dimethylformamide (1.5 mL) was sequentially treated with 2-chloro-6-fluoro-3-(propylsulfonamido)benzoic acid (48.9 mg, 0.165 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31.7 mg, 0.165 mmol), and 1-hydroxybenzotriazole (22.3 mg, 0.165 mmol) at ambient temperature. After 24 hours, the reaction mixture was diluted with ethyl acetate and washed with water (4×), sodium bicarbonate (2×), and brine (1×), dried over sodium sulfate and concentrated. The crude product was triturated with dichloromethane to provide 2-chloro-6-fluoro-3-(propylsulfonamido)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide (61.7 mg, 0.0382 mmol, 25.4% yield) as a solid. 1H NMR (400 MHz, CD3OD) δ 8.40-8.35 (d, 2H), 7.73-7.67 (q, 1H), 7.45-7.42 (d, 1H), 7.31-7.25 (t, 1H), 6.53-6.50 (d, 1H), 3.15-3.08 (t, 2H), 1.93-1.82 (m, 2H), 1.08-1.02 (t, 3H); MS (APCI-neg) m/z=409.1 (M-H).

Workup

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

Sources & evidence

ORD record
ord-aabaecbd3fe4439a8395ed3569bb0c18
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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