Tetrahydrofuran → (2R,4S)-ethyl 5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate

HRID 2384057Notes

Reaction equation

HRID 2384057 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:24][C:25](=[O:30])[C:26]([NH:28][NH2:29])=[O:27])[CH2:16][CH:17]([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C1C[O:34][CH2:33]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:24][C:25]([C:26]3[O:27][C:33](=[O:34])[NH:29][N:28]=3)=[O:30])[CH2:16][C@@H:17]([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 59608105(4S)-ethyl 5-(3'-chlorobiphenyl-4-yl)-4-(2-hydrazinyl-2-oxoacetamido)-2-methylpentanoate

Product 1

HCID 59608150(2R,4S)-ethyl 5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate

Procedure

To a solution of (4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-4-(2-hydrazinyl-2-oxoacetamido)-2-methylpentanoate, intermediate 26, (542 mg, 1.25 mmol) in THF (16 mL) is added CDl (244 mg, 1.50 mmol) at room temperature. After stirring for 18 hour at room temperature, the reaction is quenched with H2O and 1M HCl and diluted in 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 by Chiral-HPLC (OJ-H 21×250 mm, EtOH(0.1% TFA)/Heptane=30/70) to give (2R,4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate (333 mg). HPLC retention time=1.74 minutes (condition A); MS 458.2 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (d, J=7.1 Hz, 3H) 1.12 (t, J=7.1 Hz, 3H) 1.58-1.74 (m, 1H) 1.76-1.91 (m, 1H) 2.45-2.50 (m, 1H) 2.77 (dd, J=13.7, 7.9 Hz, 1H) 2.86 (dd, J=13.7, 7.9 Hz, 1H) 4.00 (q, J=7.1 Hz, 2H) 4.06-4.22 (m, 1H) 7.28 (d, J=8.1 Hz, 2H) 7.37-7.42 (m, 1H) 7.47 (t, J=7.8 Hz, 1H) 7.58-7.66 (m, 3H) 7.67-7.73 (m, 1H) 8.86 (d, J=8.8 Hz, 1H) 12.95 (s, 1H).

Workup

  1. customthe reaction is quenched with H2O and 1M HCl
  2. additiondiluted in 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) and by Chiral-HPLC (OJ-H 21×250 mm, EtOH(0.1% TFA)/Heptane=30/70)

Sources & evidence

ORD record
ord-3c3f2a061023489f83caff85e76983eb
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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