2-Dimethylaminopyridine → N-{1-[2,6-dichloro-4-(hydroxymethyl)benzoyl]-1H-pyrrolo[3,2-c]pyridin-4-yl}cyclopropanecarboxamide

HRID 2201861Notes

Reaction equation

HRID 2201861 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH2:11][OH:12])[CH:8]=[C:7]([Cl:13])[C:3]=1[C:4]([OH:6])=O.ON1C2N=CC=CC=2N=N1.CN(C1C=CC=CN=1)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[NH:66]1[C:74]2[CH:73]=[CH:72][N:71]=[C:70]([NH:75][C:76]([CH:78]3[CH2:80][CH2:79]3)=[O:77])[C:69]=2[CH:68]=[CH:67]1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CC=CC=1.O>[Cl:13][C:7]1[CH:8]=[C:9]([CH2:11][OH:12])[CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([N:66]1[C:74]2[CH:73]=[CH:72][N:71]=[C:70]([NH:75][C:76]([CH:78]3[CH2:79][CH2:80]3)=[O:77])[C:69]=2[CH:68]=[CH:67]1)=[O:6]

Participants

9

Reactant 6

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 667205832,6-Dichloro-4-(hydroxymethyl)benzoic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86720627N-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropanecarboxamide

Product 1

HCID 71618677N-{1-[2,6-dichloro-4-(hydroxymethyl)benzoyl]-1H-pyrrolo[3,2-c]pyridin-4-yl}cyclopropanecarboxamideYield 11.2%

Reagents, catalysts & solvents 2

HCID 949N,N-DimethylanilineSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 2,6-dichloro-4-(hydroxymethyl)benzoic acid (219 mg, 0.99 mmol), 1-hydroxy-7-azabenzotriazole (202 mg, 1.48 mmol), dimethylaminopyridine (60 mg, 0.49 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (567 mg, 1.48 mmol) in N,N-dimethylaniline, N-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropanecarboxamide (200 mg, 0.99 mmol) was added followed by N,N-diisopropylethylamine (0.25 ml, 1.48 mmol). The reaction mixture was stirred at room temperature for 15 hours. The contents were diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude compound was purified by silica gel column chromatography using methanol in dichloromethane (3%) as eluent to yield N-{1-[2,6-dichloro-4-(hydroxymethyl)benzoyl]-1H-pyrrolo[3,2-c]pyridin-4-yl}cyclopropanecarboxamide (45 mg, 11°/o).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude compound was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-54cad63a9521450283e008aa646cd968
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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