2-[1(S)-{(1,1-Dimethylethoxy)carbonylamino}-2-phenylethyl]-1-(2-oxo-butyl)-4-phenyl-1H-imidazole → HCID 178420743, compound

HRID 23371Notes

Reaction equation

HRID 23371 reaction equation
CC(C)(OC(N[C@H]([C:16]1[N:17](CC(=O)CC)[CH:18]=[C:19](C2C=CC=CC=2)[N:20]=1)CC1C=CC=CC=1)=O)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH:17]1[C:18]2=[N:17][CH:18]=[CH:19][NH:20][CH:19]2[NH:20][CH2:16]1

Participants

4

Reactant 1

HCID 207565832-[1(S)-{(1,1-Dimethylethoxy)carbonylamino}-2-phenylethyl]-1-(2-oxo-butyl)-4-phenyl-1H-imidazole

Product 1

HCID 178420743HCID 178420743, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent2×

Conditions

Temperature
20 °C

Procedure

2-[1(S)-{(1,1-Dimethylethoxy)carbonylamino}-2-phenylethyl]-1-(2-oxo-butyl)-4-phenyl-1H-imidazole (60 mg) in a mixture of 10% TFA in DCM was stirred at about 20° C. for about 3 hours and then concentrated under reduced pressure. The resulting intermediate dihydro-imidazo-pyrazine was dissolved in methanol and borohydride supported on resin (AMBERLITE® IRA 400, Aldrich, 2.5 mmol SH4−/g; 4 eq) was added. The pH was maintained at about 5 by addition of drops of TFA. After about 2 hours of stirring at about 20° C., the mixture was filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (ethyl acetate/Heptane 7:3; Rf=0.30). The tetrahydro-imidazopyrazine was obtained as a single diastereoisomer in 86% yield (38 mg). NMR (1H, 400 MHz, CDCl3) δ: 7.80-7.10 (m, 1 1H, arom. H), 4.28 (dd, 1H, 3J=10 Hz, 3J=3 Hz, H8), 3.95 (dd, 1H, 2J=11.5 Hz, 3J=3.6 Hz), 3.85 (dd, 1H, 2J=13.6 Hz, 3J=3.0 Hz), 3.60 (t, 1H, 2J=3J=11.5 Hz), 3.85 (dd, 1H, 2J=13.6 Hz, 3J=10 Hz), 2.98 (m, 2H), 1.85 (s, 1H, NH), 1.55 (m, 2H, CH2), 0.95 (t, 3H, CH3). NMR (13C, 100 MHz, CDCl3): 146.3, 140.9, 138.0, 134.4, 129.4, 128.6, 128.5, 126.6, 126.5, 124.8, 113.8, 55.9, 54.4, 50.2, 40.0, 26.6, 10.0. LC/MS: calculated MW=317.43, m/z=318.20 (M+H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting intermediate dihydro-imidazo-pyrazine was dissolved in methanol
  3. additionwas added
  4. stirringAfter about 2 hours of stirring at about 20° C.
  5. filtrationthe mixture was filtered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (ethyl acetate/Heptane 7:3; Rf=0.30)

Sources & evidence

ORD record
ord-c1c17654786747dfb357033a993c7dab
Source dataset
uspto-grants-2005_02
Patent number
US06852725B1

Reaction notes

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