Propionic Acid → N-(4-Bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamide

HRID 714046Notes

Reaction equation

HRID 714046 reaction equation
[Br:1][C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH2:11])[C:4]=2[CH:5]=[N:6][CH:7]=1.[C:12](O)(=[O:15])[CH2:13][CH3:14].CCN=C=NCCCN(C)C.OP([O-])(O)=O.[K+]>C(Cl)Cl>[Br:1][C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])[C:4]=2[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 1032Propionic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516951Monobasic potassium phosphateHCID 717438934-Bromo-6,7-dihydro-5H-cyclopenta[C]pyridin-7-amine

Product 1

HCID 86685956N-(4-Bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamideYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred black solution of (rac)-4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-amine (intermediate A-4 [C]) (213 mg, 1 mmol) and propionic acid (82.1 μL, 1.1 mmol) in CH2Cl2 (5.0 mL) at 0° C. was added EDCI (230 mg, 1.2 mmol), stirring was continued over night and the reaction mixture was allowed to warm up to RT. The reaction mixture was poured on aq. 10% KH2PO4 solution followed by extraction with AcOEt (3×). The organic phases were washed once with aq. 10% KH2PO4, aq. sat. NaHCO3 and aq. sat. NaCl solution. The combined organic phases were dried over Na2SO4, filtered, evaporated and purified by flash chromatography (75 g SiO2, Telos-cartridge, CH2Cl2/MeOH (2%)) to afford the title compound (105 mg, 39%) as a dark grey solid. MS: 269.0 (M+H+, 1 Br).

Workup

  1. waitwas continued over night
  2. extractionfollowed by extraction with AcOEt (3×)
  3. washThe organic phases were washed once with aq. 10% KH2PO4, aq. sat. NaHCO3 and aq. sat. NaCl solution
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash chromatography (75 g SiO2, Telos-cartridge, CH2Cl2/MeOH (2%))

Sources & evidence

ORD record
ord-22b68fb11f3b49a0bc6960d0e837e829
Source dataset
uspto-grants-2015_11
Patent number
US09187429B2

Reaction notes

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