4-Iodo-1-tritylimidazole → HCID 68705849, compound

HRID 2261920Notes

Reaction equation

HRID 2261920 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.C([Mg]Br)C.[C:30]([O:34][C:35]([NH:37][C@:38]([C:47]1[O:51][C:50]([C:52]2[CH:53]=[C:54]([N:59]([CH3:64])[S:60]([CH3:63])(=[O:62])=[O:61])[CH:55]=[C:56](Br)[CH:57]=2)=[N:49][N:48]=1)([CH3:46])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31]>[Cl-].[Zn+2].[Cl-].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>[C:30]([O:34][C:35]([NH:37][C@:38]([C:47]1[O:51][C:50]([C:52]2[CH:53]=[C:54]([N:59]([CH3:64])[S:60]([CH3:63])(=[O:62])=[O:61])[CH:55]=[C:56]([C:2]3[N:3]=[CH:4][N:5]([C:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:6]=3)[CH:57]=2)=[N:49][N:48]=1)([CH3:46])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 6182524-Iodo-1-tritylimidazoleHCID 58990121HCID 58990121, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 68705849HCID 68705849, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a solution of 4-iodo-1-trityl-1H-imidazole (Preparation described in Jetter, M. C., Boyd, R. E., Reitz, A. B. Org. Prep. Proced. Int. 1996, 28(6), 709-710; 87 mg, 0.20 mmol) in 2 mL TF was added ethylmagnesium bromide (1.0 M solution in THF, 0.24 mL, 0.24 mmol) dropwise. The reaction was stirred at rt for 0.5 h and zinc chloride (0.5 M solution in THF, 0.8 mL, 0.4 mmol) was added. After stirring for 1 h, 3-(5-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)-1,3,4-oxadiazol-2-yl)-5-bromo-N-methyl-N-(methylsulfonyl)benzenamine (100 mg, 0.18 mmol) and tetrakis(triphenylphosphine)palladium(0) (20.8 mg, 0.018 mmol) were added. The mixture was heated in a microwave oven to 80° C. for 0.5 h, quenched with saturated ammonium chloride and extracted with EtOAc. The combined organic layers were washed with water and brine. Drying, solvent evaporation and flash chromatography (15-65% EtOAc/hexanes) gave 3-(5-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)-1,3,4-oxadiazol-2-yl)-N-methyl-N-(methylsulfonyl)-5-(1-trityl-1H-imidazol-4-yl)benzenamine. 1H NMR (CDCl3) δ 8.23 (s, 1H), 7.98 (s, 1H), 7.87 (s, 1H), 7.54 (d, J=0.8 Hz, 1H), 7.40-7.00 (m, 21H), 3.56 (d, J=12 Hz, 1H), 3.44 (d, J=12 Hz, 1H), 3.39 (s, 3H), 2.92 (s, 3H), 1.72 (s, 3H), 1.41 (s, 9H).

Workup

  1. stirringAfter stirring for 1 h
  2. temperatureThe mixture was heated in a microwave oven to 80° C. for 0.5 h
  3. customquenched with saturated ammonium chloride
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with water and brine
  6. customDrying
  7. customsolvent evaporation and flash chromatography (15-65% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2af981380f574660b179debcfef22c60
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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