Methyl(4-aminophenoxy)acetate → methyl 2-[4-[[2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]amino]phenoxy]acetate

HRID 1508679Notes

Reaction equation

HRID 1508679 reaction equation
[NH2:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.Cl.Cl[C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[N:19]=[C:18]2[CH2:29][CH2:30][CH2:31][C:17]=12>CO.ClCCl>[Cl:28][C:24]1[CH:23]=[C:22]([C:20]2[N:19]=[C:18]3[CH2:29][CH2:30][CH2:31][C:17]3=[C:16]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[CH:12][CH:13]=3)[CH:21]=2)[CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 6422115Methyl(4-aminophenoxy)acetateHCID 901118224-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine HCl salt

Product 1

HCID 90112439methyl 2-[4-[[2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]amino]phenoxy]acetateYield 44%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

An 18-mL vial was charged with methyl 2-(4-aminophenoxy)acetate (24 mg, 0.13 mmol, 2 eq.) and 4-Chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine HCl salt (20 mg, 0.066 mmol, 1 eq. See step 1 of EXAMPLE 1). The mixture was dissolved in a mixture of MeOH (1 ml) and dichloromethane (2 ml). After the volatile material was removed under reduced pressure, the residue was heated at 150° C. under argon for 1 hr. After cooling to room temperature, the reaction mixture was partitioned between NaHCO3 aq. (10 ml) and ethyl acetate (10 ml). The organics was separated and dried over MgSO4. The solvent was removed under reduced pressure to give a residue, which was purified by chromatography on silica gel using dichloromethane followed by 0.1˜0.3% methanol in dichloromethane as eluent to give the desired product methyl 2-[4-[[2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl]amino]phenoxy]acetate as white solid (11.8 mg, 44% yield).

Workup

  1. customAfter the volatile material was removed under reduced pressure
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between NaHCO3 aq. (10 ml) and ethyl acetate (10 ml)
  4. customThe organics was separated
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed under reduced pressure
  7. customto give a residue, which
  8. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-bdb336c843634f49a2e9bda1856c05db
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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