4-Iodo-1-tritylimidazole → HCID 67207459, compound

HRID 1023873Notes

Reaction equation

HRID 1023873 reaction equation
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.CC[Mg+].[Br-].I[C:31]1[CH:51]=[CH:50][CH:49]=[CH:48][C:32]=1[CH2:33][CH2:34][C@H:35]1[C:40]([O:41][CH3:42])=[N:39][C@H:38]([CH:43]([CH3:45])[CH3:44])[C:37]([O:46][CH3:47])=[N:36]1>C1COCC1.C(Cl)Cl.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:43]([C@@H:38]1[C:37]([O:46][CH3:47])=[N:36][C@@H:35]([CH2:34][CH2:33][C:32]2[CH:31]=[CH:51][CH:50]=[CH:49][C:48]=2[C:2]2[N:3]=[CH:4][N:5]([C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:6]=2)[C:40]([O:41][CH3:42])=[N:39]1)([CH3:45])[CH3:44]

Participants

8

Reactant 3

HCID 6182524-Iodo-1-tritylimidazoleHCID 67207183HCID 67207183, compoundHCID 178461630HCID 178461630, compound

Product 1

HCID 67207459HCID 67207459, compoundYield 29%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-iodo-1-trityl-1H-imidazole (300 mg, 0.688 mmol) in anhydrous THF (4 mL) at room temperature was added EtMgBr (1.0 M in THF, 0.802 mmol, 0.8 mL) dropwise, under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and anhydrous ZnCl2 (109 mg, 0.802 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of the (2S,5R)-2-(2-iodophenethyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (237 mg, 0.573 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (33 mg, 0.029 mmol). The reaction mixture was allowed to stir at 70° C. for 12 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2Cl2 (10 mL) and the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (87 mg, 0.146 mmol, 29%). 1H NMR: 0.70 (d, 3H, J=6 Hz), 1.02 (d, 3H, J=7.2 Hz), 1.72-1.81 (m, 1H), 2.01-2.08 (m, 1H), 2.15-2.24 (m, 1H), 2.80-3.09 (m, 2H), 3.54 (s, 3H), 3.56 (s, 3H), 3.86-3.91 (m, 214), 6.94 (d, 1H, J=1.2 Hz), 7.15-7.22 (m, 9H), 7.27 (d, 1H, J=1.6 Hz), 7.32-7.36 (m, 8H), 7.48 (d, 1H, J=1.2 Hz), 7.58-7.61 (m, 1H).

Workup

  1. stirringto stir for 90 min
  2. stirringto stir at 70° C. for 12 h under an atmosphere of N2
  3. washthe organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-24b60a1906424563be835ffaff5c26ce
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

Loading…