Tetrahydrofuran → HCID 59607837, compound

HRID 70838Notes

Reaction equation

HRID 70838 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:22][C:23](=[O:28])[C:24]([NH:26][NH2:27])=[O:25])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C1C[O:32][CH2:31]C1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:22][C:23]([C:24]3[O:25][C:31](=[O:32])[NH:27][N:26]=3)=[O:28])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 59607746HCID 59607746, compound

Product 1

HCID 59607837HCID 59607837, compound

Procedure

To a solution of (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(2-hydrazinyl-2-oxoacetamido)butanoate, intermediate 12, (289 mg, 0.72 mmol) in THF (8.5 mL) is added CD (139 mg, 0.86 mmol) at room temperature. After stirring for 18 hour at room temperature, the reaction is quenched with H2O and 1M HCl, and the crude is diluted with EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) and then lyophilized to give (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)butanoate (100 mg). HPLC retention time=1.67 minutes (condition A); MS (m+1)=430.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.1 Hz, 3 H) 2.52-2.70 (m, 2 H) 2.84 (dd, J=13.7, 8.4 Hz, 1 H) 2.90 (dd, J=13.7, 8.4 Hz, 1 H) 4.02 (q, J=7.1 Hz, 2 H) 4.42-4.58 (m, 1 H) 7.30 (d, J=8.1 Hz, 2 H) 7.37-7.43 (m, 1 H) 7.47 (t, J=7.8 Hz, 1 H) 7.57-7.66 (m, 3 H) 7.70 (t, J=1.9 Hz, 1 H) 8.98 (d, J=8.8 Hz, 1 H) 12.94 (s, 1 H).

Workup

  1. customthe reaction is quenched with H2O and 1M HCl
  2. additionthe crude is diluted with EtOAc
  3. washThe organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-b5f05519e0274fababd212ed676063b6
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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