2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide → HCID 178485249, compound

HRID 595684Notes

Reaction equation

HRID 595684 reaction equation
Br[C:2]1[N:3]=[C:4]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[C:15]([F:18])[CH:14]=[CH:13][CH:12]=3)[C:5]([OH:8])=[N:6][CH:7]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:27][C:28]3[CH:38]=[C:37]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])[C:36](B4OC(C)(C)C(C)(C)O4)=[CH:35][C:29]=3[C:30]=2[C:31]([NH:33][CH3:34])=[O:32])=[CH:22][CH:21]=1>CC(O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:18][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:16]=1[CH:17]=[C:9]([C:4]1[N:3]=[C:2]([C:36]3[C:37]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:38][C:28]4[O:27][C:26]([C:23]5[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=5)=[C:30]([C:31]([NH:33][CH3:34])=[O:32])[C:29]=4[CH:35]=3)[CH:7]=[N:6][C:5]=1[OH:8])[NH:10]2

Participants

7

Reactant 2

HCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 178517600HCID 178517600, compound

Product 1

HCID 178485249HCID 178485249, compoundYield 41.6%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyrazin-2-ol (prepared using similar method described in Example 1, 1.23 g, 3.98 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (2 g, 3.98 mmol) and K3PO4.3H2O (2.12 g, 7.96 mmol) in IPA (20 mL) and H2O (2 mL) was added Pd2(dba)3 (50 mg) and X-Phos (50 mg) under nitrogen atmosphere. The reaction mixture was stirred at 100° C. for 16 h, concentrated in vacuo to remove IPA. The residue was diluted with H2O and extracted with DCM. Then the combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, concentrated and purified by column chromatography (PE:EA=1:2) to give 5-(6-(4-fluoro-1H-indol-2-yl)-5-hydroxypyrazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (1 g, yield: 41%). 1H-NMR (CDCl3, 400 MHz) δ 8.52 (d, J=4.0 Hz, 1H), 8.06 (s, 1H), 8.02 (s, 1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.42 (t, J=8.8 Hz, 2H), 7.33˜7.36 (m, 2H), 7.11˜7.18 (m, 2H), 6.80 (dd, J1=10.4 Hz, J2=8.0 Hz, 2H), 3.27 (s, 3H), 3.10 (s, 3H), 2.85 (d, J=4.8 Hz, 3H). MS (M+H)+: 604.

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove IPA
  3. additionThe residue was diluted with H2O
  4. extractionextracted with DCM
  5. washThen the combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by column chromatography (PE:EA=1:2)

Sources & evidence

ORD record
ord-f181bb2832d0436aa3de45a32368fed1
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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