Imidazole → HCID 68706459, compound

HRID 2261921Notes

Reaction equation

HRID 2261921 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[C:11]([O:15][C:16]([NH:18][C@:19]([C:28]1[O:32][C:31]([C:33]2[CH:34]=[C:35]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[CH:36]=[C:37](Br)[CH:38]=2)=[N:30][N:29]=1)([CH3:27])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>C1COCC1.[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>[CH3:35][N:40]([CH3:45])[S:41]([N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:37]1[CH:36]=[C:35]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[CH:34]=[C:33]([C:31]2[O:32][C:28]([C@@:19]([NH:18][C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])([CH3:27])[CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:29][N:30]=2)[CH:38]=1)(=[O:43])=[O:42]

Participants

7

Reactant 3

HCID 795ImidazoleHCID 58990121HCID 58990121, compoundHCID 178418339Butyllithium

Product 1

HCID 68706459HCID 68706459, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N,N-dimethylsulfamoyl)imidazole (Preparation described in Winter, J., Retey, J. Synthesis. 1994, 3, 245-246; 47 mg, 0.27 mmol) in 1 mL THF, cooled to −78° C. was added n-butyllithium (2.5 M solution in hexanes, 0.12 mL, 0.29 mmol) dropwise. The reaction was stirred at −78° C. for 15 min and zinc chloride (0.5 M solution in THF, 1.6 mL, 0.81 mmol) was added. After warming to rt over 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 0.75 h, quenched with water and extracted with EtOAc. The combined organic layers were washed with brine. Drying, solvent evaporation and flash chromatography (50-100% EtOAc/hexanes) gave 3-(1-(dimethylsulfamoyl)-1H-imidazol-2-yl)-5-(5-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)-1,3,4-oxadiazol-2-yl)-N-methyl-N-(methylsulfonyl)benzenamine. 1H NMR (CDCl3) δ 8.26 (m, 1H), 8.15 (m, 1H), 7.87 (m, 1H), 7.49 (d, J=1.6 Hz, 1H), 7.26 (m, 3H), 7.18 (d, J=1.6 Hz, 1H), 7.08 (m, 2H), 3.60 (d, J=12 Hz, 1H), 3.40 (m, 4H), 2.95 (s, 3H), 2.64 (s, 6H), 1.71 (s, 3H), 1.42 (bs, 9H).

Workup

  1. temperatureAfter warming to rt over 1 h
  2. temperatureThe mixture was heated in a microwave oven to 80° C. for 0.75 h
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. customDrying
  7. customsolvent evaporation and flash chromatography (50-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f243db13b34c4f76ab58b228eb6227ad
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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