1,1'-Carbonyldiimidazole → HCID 59608291, compound

HRID 1469633Notes

Reaction equation

HRID 1469633 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.C1N=CN([C:35](N2C=NC=C2)=[O:36])C=1>C1COCC1>[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:35](=[O:36])[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

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 59608162HCID 59608162, compound

Product 1

HCID 59608291HCID 59608291, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 CDI (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=7.1Hz, 3H), 1.22 (t, J=7.1Hz, 3H), 1.66 (ddd, J=14.3, 10.2, 3.8Hz, 1H), 2.02 (ddd, J=14.2, 10.0, 3.8Hz, 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=8.8Hz, 1H), 7.25 (d, 1H), 7.28-7.35 (m, 1H), 7.40 (t, J=7.6Hz, 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-de79a89240fa4ae59c3047214bd7ff9d
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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