Sodium Carbonate → HCID 57330783, compound

HRID 1754353Notes

Reaction equation

HRID 1754353 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:27]([O:29]CC)=[O:28])[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[C:23](=[O:24])[C:22]([CH3:26])([CH3:25])[O:21][N:20]=3)[CH:14]=2)=[CH:11][CH:12]=1)=[O:5].C(OC(=O)C1C=C(NC(=O)C2C(F)=CC=CC=2F)C=CC=1Br)C.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[F:36][C:32]1[CH:33]=[CH:34][CH:35]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:27]([OH:29])=[O:28])[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[C:23](=[O:24])[C:22]([CH3:25])([CH3:26])[O:21][N:20]=3)[CH:14]=2)=[CH:11][CH:12]=1)=[O:5]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 67515141HCID 67515141, compoundHCID 67517252HCID 67517252, compound

Product 1

HCID 57330783HCID 57330783, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Step-2: Ethyl 4-(2,6-difluorobenzamido)-3′-(5,5-dimethyl-4-oxo-4,5-dihydroisoxazol-3-yl)-[1,1′-biphenyl]-2-carboxylate: To a solution of ethyl-2-bromo-5-(2,6-difluorobenzamido)benzoate (180 mg, 0.47 mmol, 1.0 eq), in dioxane (5 mL), successively intermediate 9 (150 mg, 0.47 mmol, 1.0 eq) sodium carbonate (100 mg, 0.95 mmol, 2 eq) and Pd(PPh3)2Cl2 (33 mg, 0.047 mmol, 0.1 eq) were added. The resulting solution was thoroughly deoxygenated by subjecting to vacuum/nitrogen cycle three times and the reaction mixture was then heated at 120° C. in microwave (Biotage) for 30 min. The resulting mixture was cooled to room temperature, diluted with ethyl acetate (10 mL) and filtered through celite. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, ethyl acetate in hexane system as eluent) to afford 90 mg of the title compound as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.13-8.09 (m, 2H), 8.05-8.01 (m, 2H), 7.88 (s, 1H, D2O exchangeable), 7.52-7.42 (m, 4H), 7.04 (t, J=8.0 Hz, 2H), 4.14 (q, J=7.0 Hz, 2H), 1.49 (s, 6H), 1.09 (t, J=7.0 Hz, 3H); ESI-MS (m/z) 493 (MH)+.

Workup

  1. customThe resulting solution was thoroughly deoxygenated
  2. temperatureThe resulting mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (10 mL)
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate in hexane system as eluent)

Sources & evidence

ORD record
ord-9cb2f42191a24c62a9a756d0d6629820
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

Loading…