Potassium Carbonate → HCID 178501954, compound

HRID 889562Notes

Reaction equation

HRID 889562 reaction equation
[CH3:1][O:2][C:3](=[O:33])[NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([C@@H:17]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[NH:14][C:15]=2Cl)=[CH:7][CH:6]=1.COC(NC1C=CC(B(O)O)=CC=1)=O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O>[CH3:1][O:2][C:3](=[O:33])[NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([C@@H:17]([NH:25][C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[NH:14][CH:15]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27734944-(Methoxycarbonylamino)phenylboronic acidHCID 57976328HCID 57976328, compound

Product 1

HCID 178501954HCID 178501954, compound

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

{4-[2-((S)-1-tert-butoxycarbonylamino-2-phenyl-ethyl)-5-chloro-1H-imidazol-4-yl]-phenyl}-carbamic acid methyl ester: To 92E (4.5 g, 12.2 mmol) were added 4-(methoxycarbonylamino)-phenyl boronic acid (2.97 g, 15.0 mmol), and potassium carbonate (5 g, 36 mmol). To this mixture was added 4:1 DME/water (100 mL) that had been degassed with N2. Tetrakis[(triphenyl)phosphine]palladium (0.7 g, 0.61 mmol) was added and the reaction was heated at 80° C. for 24 h. The reaction was cooled and solvents removed in vacuo. The residue was partitioned with ethyl acetate/water and the layers separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration afforded {4-[2-((S)-1-tert-butoxycarbonylamino-2-phenyl-ethyl)-1H-imidazol-4-yl]-phenyl}-carbamic acid methyl ester as a yellow foam (8.1 g). LCMS m/z 437.02 (M+H)+. To this intermediate (5.3 g, 12.2 mmol) in acetonitrile (60 mL) was added N-chlorosuccinimide (1.8 g, 13.4 mmol), and the reaction was heated to 55° C. for 24 h. The solvent was removed in vacuo, the residue was partitioned with ethyl acetate/saturated aqueous sodium carbonate, and the layers separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine and dried (MgSO4). Purification by silica gel chromatography (hexane/ethyl acetate) afforded 92F (1.92 g, 33.6% over 2 steps) as a yellow foam. LCMS m/z 471.3 (M+H)+. 1HNMR (400 MHz, CDCl3) δ: 1.39 (s, 9 H), 3.30 (d, J=7.07 Hz, 2 H) 3.79 (s, 3 H), 4.85 (d, J=7.58 Hz, 1 H), 5.20 (d, J=7.58 Hz, 1 H), 6.68 (s, 1 H), 7.14-7.32 (m, 4 H), 7.38-7.56 (m, 5 H).

Workup

  1. customhad been degassed with N2
  2. temperatureThe reaction was cooled
  3. customsolvents removed in vacuo
  4. customThe residue was partitioned with ethyl acetate/water
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-25d3852ee3b1454c92bb9b472d9a777c
Source dataset
uspto-grants-2012_08
Patent number
US08252830B2

Reaction notes

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