Diisopropylethylamine → 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)-N-ethylbenzamide

HRID 2201854Notes

Reaction equation

HRID 2201854 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:15])[NH:12][CH2:13][CH3:14])[CH:8]=[C:7]([Cl:16])[C:3]=1[C:4]([OH:6])=O.ON1C2N=CC=CC=2N=N1.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:60]1[C:68]2[CH:67]=[CH:66][N:65]=[C:64]([NH:69][C:70]([CH:72]3[CH2:74][CH2:73]3)=[O:71])[C:63]=2[CH:62]=[CH:61]1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CC=CC=1.O>[Cl:16][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([N:60]1[C:68]2[CH:67]=[CH:66][N:65]=[C:64]([NH:69][C:70]([CH:72]3[CH2:73][CH2:74]3)=[O:71])[C:63]=2[CH:62]=[CH:61]1)=[O:6])[C:11]([NH:12][CH2:13][CH3:14])=[O:15]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 710615382,6-Dichloro-4-(ethylcarbamoyl)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 716186153,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)-N-ethylbenzamideYield 26.6%

Reagents, catalysts & solvents 2

HCID 949N,N-DimethylanilineSolventHCID 962WaterSolvent

Procedure

A well stirred mixture of 2,6-dichloro-4-(ethylcarbamoyl)benzoic acid (84.6 mg, 0.42 mmol), 1-hydroxy-7-azabenzotriazole (77 mg, 0.57 mmol), N,N-dimethyl aminopyridine (22 mg, 0.11 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (216 mg, 0.57 mmol) in N,N-dimethylaniline was treated with N-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropanecarboxamide (100 mg, 0.38 mmol) and N,N-diisopropylethylamine (0.1 ml, 0.95 mmol). The reaction was stirred overnight at room temperature. The contents were diluted with water and extracted with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography using methanol in dichloromethane (3%) as eluent to yield 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)-N-ethylbenzamide (45 mg, 26%) as an off white solid.

Workup

  1. stirringThe reaction was stirred overnight at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organic portion was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-75cc998b079940d7bb1d04eed81dd4f6
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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