Tetrahydrofuran → HCID 59608291, compound

HRID 2384055Notes

Reaction equation

HRID 2384055 reaction equation
[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17][C:18](=[O:23])[C:19]([NH:21][NH2:22])=[O:20])[CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3][CH:2]=1.C1C[O:33][CH2:32]C1>>[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17][C:18]([C:19]2[O:20][C:32](=[O:33])[NH:22][N:21]=2)=[O:23])[CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3][CH:2]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 59608162HCID 59608162, compound

Product 1

HCID 59608291HCID 59608291, compound

Procedure

To a solution of (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-hydrazinyl-2-oxoacetamido)-2-methylpentanoate, intermediate 24, (200 mg, 0.50 mmol) in THF (10 mL) is added CDl (86 mg, 0.53 mmol). The crude is stirred at room temperature for 4 hrs. The crude is heated to 60 deg C. for 30 mins. This reaction is quenched with water and diluted in EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated. The crude residue is purified via HPLC MeCN/water (0.1% TFA) to give (2R,4S)-ethyl 5-(biphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate (69 mg). HPLC retention time=1.79 minutes (condition A), MS 424.2 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.17 (d, J=7.1 Hz, 3H), 1.22 (t, J=7.1 Hz, 3H), 1.66 (ddd, J=14.3, 10.2, 3.8 Hz, 1H), 2.02 (ddd, J=14.2, 10.0, 3.8 Hz, 1H), 2.59 (m, 1H), 2.89 (dd, 1H), 2.96 (dd, 1H), 4.03-4.19 (q, 2H), 4.37-4.47 (m, 1H), 6.91 (d, J=8.8 Hz, 1H), 7.25 (d, 1H), 7.28-7.35 (m, 1H), 7.40 (t, J=7.6 Hz, 2H), 7.49-7.60 (m, 4H), 10.51 (br. s., 1H).

Workup

  1. temperatureThe crude is heated to 60 deg C
  2. waitfor 30 mins
  3. customThis reaction is quenched with water
  4. additiondiluted in EtOAc
  5. washThe organic layer is washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue is purified via HPLC MeCN/water (0.1% TFA)

Sources & evidence

ORD record
ord-6c0c55c5e8624d2392f12af498092a99
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

Loading…