Cesium carbonate → 5-(6-chloro-5-(3-hydroxypropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595740Notes

Reaction equation

HRID 595740 reaction equation
C([CH:3]([OH:14])[CH2:4][CH2:5][C:6]1[C:7]([Cl:13])=[N:8][C:9](Cl)=[CH:10][CH:11]=1)C.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[O:23][C:24]3[CH:34]=[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[C:32](B4OC(C)(C)C(C)(C)O4)=[CH:31][C:25]=3[C:26]=2[C:27]([NH:29][CH3:30])=[O:28])=[CH:18][CH:17]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C1(C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.O1CCOCC1>[Cl:13][C:7]1[N:8]=[C:9]([C:32]2[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])=[CH:34][C:24]3[O:23][C:22]([C:19]4[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=4)=[C:26]([C:27]([NH:29][CH3:30])=[O:28])[C:25]=3[CH:31]=2)[CH:10]=[CH:11][C:6]=1[CH2:5][CH2:4][CH2:3][OH:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 118573558Ethyl 3-(2,6-dichloropyridin-3-yl)propan-1-olHCID 131734592XantPhos Biphenyl

Product 1

HCID 903325055-(6-chloro-5-(3-hydroxypropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of ethyl 3-(2,6-dichloropyridin-3-yl)propan-1-ol (180 mg, 0.873 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (439 mg, 0.873 mmol), XantPhos Biphenyl precatalyst (78 mg, 0.087 mmol), and cesium carbonate (854 mg, 2.62 mmol) was added 1,4-Dioxane (7.3 mL) and water (1.5 mL). A steady stream of N2 was bubbled through the reaction mixture for 5 minutes then the mixture was heated to 70° C. for 4 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed successively with H2O (1×) and brine (1×). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using a gradient of 0-100% EtOAc/CH2Cl2 as eluent. Further purification by preparative TLC using 50% EtOAc/CH2Cl2 as eluent provided the title compound. 1H NMR δ (ppm) (CHCl3-d): 8.01˜7.96 (3H, m), 7.72 (1H, d, J=7.68 Hz), 7.68 (1H, s), 7.56 (1H, d, J=7.70 Hz), 7.23 (2H, t, J=8.6 Hz), 5.95 (1H, br s), 3.78 (2H, q, J=5.76 Hz), 3.24 (3H, s), 3.03 (3H, d, J=4.88 Hz), 2.93 (2H, t, J=7.76 Hz), 2.88 (3H, s), 2.03˜1.97 (2H, m). MS (M+H)+: 545.

Workup

  1. customA steady stream of N2 was bubbled through the reaction mixture for 5 minutes
  2. temperatureThe mixture was cooled to ambient temperature
  3. additiondiluted with EtOAc
  4. washwashed successively with H2O (1×) and brine (1×)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. customFurther purification by preparative TLC

Sources & evidence

ORD record
ord-91ee2989e08f4c8c8f8d2e39ab4ea3aa
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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