1,2-Dichloroethane → Methyl cis-2-(3-chloro-5-(5-(2-(methoxymethyl)-2'-methylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl)pyridin-2-ylamino)cyclopentanecarboxylate

HRID 1631042Notes

Reaction equation

HRID 1631042 reaction equation
[Cl:1][C:2]1[C:3]([NH:12][C@H:13]2[CH2:17][CH2:16][CH2:15][C@H:14]2[C:18]([O:20][CH3:21])=[O:19])=[N:4][CH:5]=[C:6]([C:8](=[N:10][OH:11])[NH2:9])[CH:7]=1.Br[C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=O)=[CH:25][C:24]=1[CH2:33]OC.[CH2:36](Cl)[CH2:37]Cl>CC#N.N1C=CC=CC=1>[Cl:1][C:2]1[C:3]([NH:12][C@H:13]2[CH2:17][CH2:16][CH2:15][C@H:14]2[C:18]([O:20][CH3:21])=[O:19])=[N:4][CH:5]=[C:6]([C:8]2[N:9]=[C:33]([C:24]3[CH:23]=[CH:32][C:31]([C:5]4[CH:6]=[CH:7][CH:2]=[CH:3][C:36]=4[CH3:37])=[C:26]([CH2:27][O:29][CH3:30])[CH:25]=3)[O:11][N:10]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoateHCID 90293497cis-Methyl 2-(3-chloro-5-(n'-hydroxycarbamimidoyl)pyridin-2-ylamino)cyclopentanecarboxylate

Product 1

HCID 67135658Methyl cis-2-(3-chloro-5-(5-(2-(methoxymethyl)-2'-methylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl)pyridin-2-ylamino)cyclopentanecarboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of cis-methyl 2-(3-chloro-5-(N′-hydroxycarbamimidoyl)pyridin-2-ylamino)cyclopentanecarboxylate (0.172 g; 0.55 mmol) and Intermediate A1 (0.155 g; 0.60 mmol) in MeCN (2 mL) was added EDC (0.117 g; 0.61 mmol). The reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with pyridine (2 mL) and heated at 150° C. in the microwave for 30 minutes. The solvent was removed in vacuo and the residue dissolved in DCM. The mixture was washed with water and the organic phase passed through a hydrophobic frit. The solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (4:1) to afford the title product. 1H NMR (CDCl3, 400 MHz) δ 8.84 (1H, d, J=2 Hz), 8.40 (1H, s), 8.21 (1H, d, J=2), 8.15-8.10 (1H, m), 7.34-7.26 (4H, m), 7.13 (1H, d, J=7.5 Hz), 5.91 (1H, d, J=8.3 Hz), 4.83 (1H, m), 4.22-4.13 (2H, m), 3.63 (3H, s), 3.33 (3H, s), 3.23-3.17 (1H, m), 2.21-1.63 (9H, m).

Workup

  1. temperatureheated at 150° C. in the microwave for 30 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM
  4. washThe mixture was washed with water
  5. customThe solvent was evaporated in vacuo
  6. customThe residue was purified by flash chromatography on silica
  7. washeluting with iso-hexane/EtOAc (4:1)

Sources & evidence

ORD record
ord-fa2f0079e3c54211b6341510b726c5fa
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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