1,1'-Carbonyldiimidazole → HCID 59607837, compound

HRID 1945015Notes

Reaction equation

HRID 1945015 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.C1N=CN([C:34](N2C=NC=C2)=[O:35])C=1>C1COCC1>[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:34](=[O:35])[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

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 59607746HCID 59607746, compound

Product 1

HCID 59607837HCID 59607837, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 CDI (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, 3H) 2.52-2.70 (m, 2H) 2.84 (dd, J=13.7, 8.4 Hz, 1H) 2.90 (dd, J=13.7, 8.4 Hz, 1H) 4.02 (q, J=7.1 Hz, 2H) 4.42-4.58 (m, 1H) 7.30 (d, J=8.1 Hz, 2H) 7.37-7.43 (m, 1H) 7.47 (t, J=7.8 Hz, 1H) 7.57-7.66 (m, 3H) 7.70 (t, J=1.9 Hz, 1H) 8.98 (d, J=8.8 Hz, 1H) 12.94 (s, 1H).

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-c3b882489c784cc596128855b1534d78
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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