2-Dimethylaminopyridine → methyl 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)benzoate

HRID 2201879Notes

Reaction equation

HRID 2201879 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([Cl:15])[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:68]1[C:76]2[CH:75]=[CH:74][N:73]=[C:72]([NH:77][C:78]([CH:80]3[CH2:82][CH2:81]3)=[O:79])[C:71]=2[CH:70]=[CH:69]1.CCN(C(C)C)C(C)C>>[Cl:15][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([N:68]1[C:76]2[CH:75]=[CH:74][N:73]=[C:72]([NH:77][C:78]([CH:80]3[CH2:81][CH2:82]3)=[O:79])[C:71]=2[CH:70]=[CH:69]1)=[O:6])[C:11]([O:13][CH3:14])=[O:12]

Participants

7

Reactant 6

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 684593252,6-Dichloro-4-(methoxycarbonyl)benzoic acid2×HCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86720627N-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropanecarboxamide2×

Product 1

HCID 71061469methyl 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)benzoateYield 47%

Procedure

A stirred solution of 2,6-dichloro-4-(methoxycarbonyl)benzoic acid (750 mg, 3 mmol, intermediate 32), 1-hydroxy-7-azabenzotriazole (614 mg, 4.5 mmol), dimethylaminopyridine (183 mg, 1.5 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1170 mg, 4.5 mmol) in N,N-dimethylacatamide was treated with N-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropane carboxamide (605 mg, 3 mmol, intermediate 28) and Hunig's base (1.33 ml, 7.5 mmol). The reaction mixture was stirred at room temperature for about 1 hour and was heated at 50° C. for about 5 hours. To the reaction mixture, ice cold water was added and the precipitated solid was filtered, washed with water and dried. The solid thus obtained was purified by silica gel (100-200 mesh) column chromatography using methanol and dichloromethane gradient elution to afford methyl 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)benzoate (600 mg, 47%) as an off-white solid.

Workup

  1. temperaturewas heated at 50° C. for about 5 hours
  2. additionTo the reaction mixture, ice cold water was added
  3. filtrationthe precipitated solid was filtered
  4. washwashed with water
  5. customdried
  6. customThe solid thus obtained
  7. customwas purified by silica gel (100-200 mesh) column chromatography
  8. washmethanol and dichloromethane gradient elution

Sources & evidence

ORD record
ord-5a8b0e02d54d4293a85e02253631b618
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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