Sodium Carbonate → HCID 71680015, compound

HRID 624313Notes

Reaction equation

HRID 624313 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:7]([C:17]3[NH:18][CH:19]=[CH:20][N:21]=3)[C:6]=2[C:22]=1[F:23].[CH3:24][O:25][C:26]1[CH:43]=[C:42]([CH3:44])[C:41](B2OC(C)(C)C(C)(C)O2)=[CH:40][C:27]=1[C:28]([NH:30][C:31]1([C:34]2[N:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[CH2:33][CH2:32]1)=[O:29].C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:23][C:22]1[C:6]2[C:7]([C:17]3[NH:18][CH:19]=[CH:20][N:21]=3)=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[O:9][C:5]=2[CH:4]=[CH:3][C:2]=1[C:41]1[C:42]([CH3:44])=[CH:43][C:26]([O:25][CH3:24])=[C:27]([CH:40]=1)[C:28]([NH:30][C:31]1([C:34]2[N:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[CH2:32][CH2:33]1)=[O:29]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86691623HCID 86691623, compoundHCID 86691624HCID 86691624, compound

Product 1

HCID 71680015HCID 71680015, compoundYield 4.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 2-(5-chloro-4-fluoro-2-(4-fluorophenyl)benzofuran-3-yl)-1H-imidazole (0.1 g, 0.302 mmol) and 2-methoxy-4-methyl-N-(1-(pyrimidin-2-yl)cyclopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.186 g, 0.454 mmol) in dioxane (2 ml) in a sealed tube was added water (0.1 ml) and sodium carbonate (0.080 g, 0.756 mmol). The resulting mixture was degassed for 10 min, added with palladium (II) acetate (6.79 mg, 0.030 mmol) followed by 2-(dicyclohexyl-phosphino)-2′,4′,6′-triisopropylbiphenyl (0.144 g, 0.302 mmol) under a N2 atmosphere. The resulting mixture was again degassed for 5 minutes. The reaction mixture was then heated at 90° C. The reaction mixture was diluted with ethyl acetate, washed with water, dried over Na2SO4, filtered and concentrated. The crude product was purified by using 40 g combiflash silica column with 6% methanol in chloroform as an eluent. The desired fractions were collected and concentrated to give the titled product (8 mg, Yield: 4.6%). 1H NMR (400 MHz, CD3OD): δ 8.65 (d, J=4.8, 2H), 7.88 (s, 1H), 7.69-7.65 (m, 2H), 7.56 (d, J=8.4, 1H), 7.31-7.27 (m, 3H), 7.24-7.16 (m, 4H), 4.08 (s, 3H), 2.28 (s, 3H), 1.81-1.78 (m, 2H), 1.52-1.49 (m, 2H). 19F NMR (376.6 MHz, DMSO-d6) −113.33, −124.62. LCMS: (ES+) m/z=578.2 (M+H)+; Column—Ascentis Express C8 (5×2.1 mm-2.7 μm); Mphase A: 2% MeCN-98% H2O-10 mM NH4COOH; Mphase B: 98% MeCN-2% H20-10 mM NH4COOH; Flow=1 ML/MIN;

Workup

  1. customThe resulting mixture was degassed for 10 min
  2. customThe resulting mixture was again degassed for 5 minutes
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified
  9. customThe desired fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-092c5c08024d41f9b04162b52c490f46
Source dataset
uspto-grants-2016_04
Patent number
US09303020B2

Reaction notes

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