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

HRID 875467Notes

Reaction equation

HRID 875467 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%).

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-17ae9b15cb854de6adcbc522c8b4e2da
Source dataset
uspto-grants-2015_03
Patent number
US08980911B2

Reaction notes

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