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

HRID 875492Notes

Reaction equation

HRID 875492 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.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.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C1C=CC=CN=1)C.[NH:77]1[C:85]2[CH:84]=[CH:83][N:82]=[C:81]([NH:86][C:87](=[O:90])[CH2:88][CH3:89])[C:80]=2[CH:79]=[CH:78]1>CC(N(C)C)=O.O>[Cl:15][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([N:77]1[C:85]2[CH:84]=[CH:83][N:82]=[C:81]([NH:86][C:87](=[O:90])[CH2:88][CH3:89])[C:80]=2[CH:79]=[CH:78]1)=[O:6])[C:11]([O:13][CH3:14])=[O:12]

Participants

9

Reactant 6

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 684593252,6-Dichloro-4-(methoxycarbonyl)benzoic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86720631N-(1H-pyrrolo[3,2-c]pyridin-4-yl)propanamide

Product 1

HCID 71061320methyl 3,5-dichloro-4-{[4-(propanoylamino)-1H-pyrrolo[3,2-c]pyridin-1-yl]carbonyl}benzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A stirred solution of 2,6-dichloro-4-(methoxycarbonyl)benzoic acid (600 mg, 2.3 mmol), in dimethylacetamide (10 mL) was treated with 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1300 mg, 3.45 mmol), 1-hydroxy-7-azabenzotriazole (469 mg, 3.45 mmol), N,N-diisopropylethylamine (1.05 mL, 5.75 mmol) and dimethylaminopyridine (140 mg, 1.15 mmol) were added and the mixture was stirred at room temperature for about 1 hour. This was followed by addition of N-(1H-pyrrolo[3,2-c]pyridin-4-yl)propanamide (450 mg, 2.3 mmol) and stirring at room temperature for about 16 hours. The reaction mixture was poured into water (150 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with brine (100 mL) and organic layer was separated and dried over anhydrous sodium sulphate to give crude product which was purified by silica gel (100-200 mesh size) column chromatography using ethyl-acetate and hexane as eluting system to give pure methyl 3,5-dichloro-4-{[4-(propanoylamino)-1H-pyrrolo[3,2-c]pyridin-1-yl]carbonyl}benzoate. (250 mg, 25%)

Workup

  1. additionwere added
  2. stirringstirring at room temperature for about 16 hours
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic layer was washed with brine (100 mL) and organic layer
  5. customwas separated
  6. dry with materialdried over anhydrous sodium sulphate
  7. customto give crude product which
  8. customwas purified by silica gel (100-200 mesh size) column chromatography
  9. washas eluting system

Sources & evidence

ORD record
ord-68ac15574e3547dea9834dd1310e4b39
Source dataset
uspto-grants-2015_03
Patent number
US08980911B2

Reaction notes

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