1,2-Dimethoxyethane → HCID 11554050, compound

HRID 2113698Notes

Reaction equation

HRID 2113698 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][C@@H:22]4[CH2:26][CH2:25][O:24][CH2:23]4)[CH:14]=3)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][N:42]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.O.C(O)C>[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C:12]([C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][C@@H:22]5[CH2:26][CH2:25][O:24][CH2:23]5)[CH:14]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:3]=2)=[CH:43][N:42]=1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 68707916HCID 68707916, compound

Product 1

HCID 11554050HCID 11554050, compoundYield 82%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

1-(4-Bromophenyl)-5-{4-methoxy-3-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-1H-pyrazole (52.0 mg, 0.125 mmol), bis(triphenylphosphine)palladium(II) chloride (20 mg, 0.02 mmol), 0.1 mL of 2.00 M aqueous sodium carbonate, 2 mL of a mixture of DME, water and ethanol in a 7:3:2 ratio, and 2-methoxy-5-pyridineboronic acid (21.1 mg, 0.138 mmol) were combined in a 2.0-5.0 mL Smith Process vial. This was sealed and placed into a Personal Chemistry Emrys Optimizer, stirred for 30 seconds, and then heated to 140° C. for 300 seconds. Upon cooling, 10 mL of water and 10 mL of ethyl acetate were added and the organic layer was separated, dried over sodium sulfate, filtered and approximately 1 g of silica gel was added and the mixture was evaporated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 10% ethyl acetate in hexanes for 3 minutes, then with a linear gradient to 100% ethyl acetate over 18 minutes and then with 100% ethyl acetate for an additional 10 minutes to give 2-methoxy-5-[4-(5-{4-methoxy-3-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-1H-pyrazol-1-yl)phenyl]pyridine (45 mg, 82%) as a yellow oil. LC/MS (EI) tR 4.3 (Method C), m/z 444.1 (M++1). 1H NMR (CDCl3 300 MHz) δ 1.9 (m, 2H); 3.7-3.9 (m, 4H); 3.9 (s, 3H); 4.0 (s, 3H); 4.8 (m, 1H) 6.5 (s, 1H); 6.6 (s, 1H); 6.9 (m, 2H); 7.0 (d, 2H); 7.4 (d, 2H); 7.5 (d, 2H); 7.8 (t, 2H); 8.3 (2, 1H).

Workup

  1. customThis was sealed
  2. temperatureUpon cooling
  3. customthe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. additionapproximately 1 g of silica gel was added
  7. customthe mixture was evaporated to dryness under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel eluting with 10% ethyl acetate in hexanes for 3 minutes
  9. waitwith a linear gradient to 100% ethyl acetate over 18 minutes

Sources & evidence

ORD record
ord-3f2e0fa52dc043a6a0c4ad8867237b61
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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