1,2-Dimethoxyethane → HCID 59240051, compound

HRID 1673032Notes

Reaction equation

HRID 1673032 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([NH:15][C:16]([CH3:20])([CH3:19])[CH2:17][OH:18])=[O:14])[N:10]=[C:9]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])=[C:4]([Cl:28])[CH:3]=1.[CH3:29][S:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)(=[O:32])=[O:31].C([O-])([O-])=O.[K+].[K+].COCCOC>CCOC(C)=O.O>[Cl:28][C:4]1[CH:3]=[C:2]([C:37]2[CH:36]=[CH:35][CH:34]=[C:33]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:38]=2)[CH:7]=[CH:6][C:5]=1[N:8]1[CH:12]=[C:11]([C:13]([NH:15][C:16]([CH3:20])([CH3:19])[CH2:17][OH:18])=[O:14])[N:10]=[C:9]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59240374HCID 59240374, compound

Product 1

HCID 59240051HCID 59240051, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 mL round bottom flask attached with condenser column and magnetic stir bar was added 1-(4-bromo-2-chlorophenyl)-2-(2-chlorophenyl)-N-(1-hydroxy-2-methylpropan-2-yl)-1H-imidazole-4-carboxamide (956 mg, 1.98 mmol), 3-methylsulfonylphenyl boronic acid (435 mg, 2.18 mmol), PdCl2dppf (150 mg, 10 mol %), K2CO3 (830 mg, 6.00 mmol), 1,2-dimethoxyethane (50 mL) and H2O (13 mL). The reaction solution was allowed to stir at 80° C. for 2.5 hrs. The reaction solution was diluted with EtOAc (150 mL) and filtered through a Celite padded Buchner funnel to remove spent Pd. The filtrate was transferred to a separatory funnel and washed with aq NH4Cl (100 mL) and aq NaCl (100 mL). The organic phase was dried over Na2SO4, filtered, concentrated on the Rotavapor and chromatographed through a 25 g SiO2 column using a mobile phase gradient of 5% EtOAc to 100% EtOAc to afford 885 mg (80% yield) of the title compound. MS (ESI) 556.3, 558.3, 560.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.22 (t, J=1.7 Hz, 1H), 8.06-8.13 (m, 2H), 8.03 (s, 1H), 7.96 (d, J=7.8 Hz, 1H), 7.82 (dd, J1=7.3 Hz, J2=1.5 Hz, 1H), 7.75 (t, J=7.8 Hz, 1H), 7.60 (d, J=8.2 Hz, 2H), 7.38-7.48 (m, 3H), 5.18 (br s, 1H), 3.45 (s, 2H), 3.36 (br s, 1H), 3.31 (s, 3H), 1.37 (s, 6H).

Workup

  1. customTo a 100 mL round bottom flask attached with condenser
  2. filtrationfiltered through a Celite
  3. customto remove
  4. customThe filtrate was transferred to a separatory funnel
  5. washwashed with aq NH4Cl (100 mL) and aq NaCl (100 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated on the Rotavapor
  9. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-59523920ae744b898f22a5d8c6ed6d2b
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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