Cesium carbonate → ethyl 3-(2-chloro-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoate

HRID 595743Notes

Reaction equation

HRID 595743 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[O:24][C:25]3[CH:35]=[C:34]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])[C:33](B4OC(C)(C)C(C)(C)O4)=[CH:32][C:26]=3[C:27]=2[C:28]([NH:30][CH3:31])=[O:29])=[CH:19][CH:18]=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:1][C:2]1[C:7]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:5]=[C:4]([C:33]2[C:34]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[CH:35][C:25]3[O:24][C:23]([C:20]4[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=4)=[C:27]([C:28](=[O:29])[NH:30][CH3:31])[C:26]=3[CH:32]=2)[N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 23157101Ethyl 3-(2,6-dichloropyridin-3-yl)propanoateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 131734592XantPhos Biphenyl

Product 1

HCID 90332427ethyl 3-(2-chloro-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)pyridin-3-yl)propanoate

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)propanoate (170 mg, 0.685 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (344 mg, 0.685 mmol), XantPhos Biphenyl precatalyst (60.9 mg, 0.069 mmol), and cesium carbonate (670 mg, 2.056 mmol) was added 1,4-dioxane (5.7 mL) and H2O (1.2 mL). A steady stream of N2 was bubbled through the reaction mixture for 5 minutes then the mixture was heated to 70° C. for 16 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/Hexanes as eluent. 1H NMR δ (ppm) (CHCl3-d): 8.01˜7.96 (3H, m), 7.75 (1H, t, J=7.74 Hz), 7.69 (1H, s), 7.55 (1H, d, J=7.70 Hz), 7.27˜7.21 (2H, m) 5.91 (1H, br s), 4.19 (2H, q, J=7.12 Hz), 3.27˜3.20 (3H, m), 3.18˜3.12 (2H, m), 3.03 (3H, d, J=4.92 Hz), 2.90˜2.80 (3H, m), 2.77 (2H, t, J=7.51 Hz), 1.30 (3H, t, J=7.15 Hz). MS (M+H)+: 588.

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

Sources & evidence

ORD record
ord-89a002d0274c4063b8d30d2aa1e5e219
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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