1,2-Dimethoxyethane → HCID 59251442, compound

HRID 1466431Notes

Reaction equation

HRID 1466431 reaction equation
[F:1][C:2]([F:27])([F:26])[CH2:3][NH:4][C:5]([C:7]1[N:8]=[C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[N:10]([C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[CH:11]=1)=[O:6].[CH3:28][S:29]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30].C([O-])([O-])=O.[K+].[K+].COCCOC>CCOC(C)=O.O>[F:1][C:2]([F:27])([F:26])[CH2:3][NH:4][C:5]([C:7]1[N:8]=[C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[N:10]([C:12]2[CH:17]=[CH:16][C:15]([C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([S:29]([CH3:28])(=[O:31])=[O:30])[CH:37]=3)=[CH:14][CH:13]=2)[CH:11]=1)=[O:6]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59251248HCID 59251248, compound

Product 1

HCID 59251442HCID 59251442, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a 50 mL round bottom flask attached with Vigreux column and magnetic stir bar was added 1-(4-Bromo-phenyl)-2-(2-chloro-phenyl)-1H-imidazole-4-carboxylic acid (2,2,2-trifluoro-ethyl)-amide (249 mg, 540 μmol), 3-methylsulfonylphenyl boronic acid (130 mg, 650 μmol), PdCl2dppf (40 mg, 10 mol %), K2CO3 (260 mg, 1.90 mmol), 1,2-dimethoxyethane (14 mL) and H2O (2 mL). The reaction solution was allowed to stir at 75° C. for 2 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 2% EtOAc to 90% EtOAc to afford 212 mg (74% yield) of the title compound. MS (ES): 534 [M+H]+, 557 [M+Na]+. 1H NMR. (400 MHz, CDCl3): δ 8.13 (s, 1H), 7.99 (s, 1H), 7.92 (d, 1H), 7.65 (t, 1H), 7.57 (d, 2H), 7.52 (d, 2H), 7.41-7.34 (m, 3H), 7.24 (d, 2H), 4.11 (q, 2H), 3.08 (s, 3H); 19F NMR (400 MHz, CDCl3) 5-72.4 ppm.

Workup

  1. customTo a 50 mL round bottom flask attached with Vigreux column and magnetic stir bar
  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-4cd15e1aaf214c3aa1504f5cff5e72e9
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

Loading…