2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 117771053, compound

HRID 2201544Notes

Reaction equation

HRID 2201544 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[F:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[O:43][C:44]3[CH:54]=[C:53]([N:55]([CH3:60])[S:56]([CH3:59])(=[O:58])=[O:57])[C:52](B4OC(C)(C)C(C)(C)O4)=[CH:51][C:45]=3[C:46]=2[C:47]([NH:49][CH3:50])=[O:48])=[CH:38][CH:37]=1.[CH2:70]([O:77][C:78]1[C:79]([C:85]([O:87][CH3:88])=[O:86])=[N:80][C:81](Br)=[CH:82][CH:83]=1)[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1>O1CCOCC1.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]>[CH2:70]([O:77][C:78]1[C:79]([C:85]([O:87][CH3:88])=[O:86])=[N:80][C:81]([C:52]2[C:53]([N:55]([CH3:60])[S:56]([CH3:59])(=[O:58])=[O:57])=[CH:54][C:44]3[O:43][C:42]([C:39]4[CH:38]=[CH:37][C:36]([F:35])=[CH:41][CH:40]=4)=[C:46]([C:47](=[O:48])[NH:49][CH3:50])[C:45]=3[CH:51]=2)=[CH:82][CH:83]=1)[C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59418684Methyl 3-(benzyloxy)-6-bromopicolinateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Product 1

HCID 117771053HCID 117771053, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (45 mg, 0.05 mmol) and X-phos (48 mg, 0.1 mmol) were added to a mixture of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (500 mg, 1 mmol), methyl 3-(benzyloxy)-6-bromopicolinate (350 mg, 1.1 mmol) and K3PO4.3H2O (798 mg, 3 mmol) in 1,4-dioxane/H2O (5 mL/0.5 mL) under N2. The mixture was stirred at 80° C. for 8 h, and after being filtered through celite, the filtrate was concentrated in vacuo, diluted with water and extracted with EtOAc. The residue was purified by column chromatography (DCM:EtOAc=40:1 to 10:1) to obtain methyl 3-(benzyloxy)-6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)picolinate (540 mg, yield: 88%). 1H-NMR (CDCl3, 400 MHz) δ 7.88˜8.04 (m, 3H), 7.70 (d, J=8.8 Hz, 1H), 7.62 (s, 1H), 7.45˜7.56 (m, 3H), 7.41 (t, J=7.2 Hz, 2H), 7.32˜7.38 (m, 1H), 7.20 (t, J=8.4 Hz, 2H), 5.90 (d, J=4.0 Hz, 1H), 5.27 (s, 2H), 3.97 (s, 3H), 3.22 (s, 3H), 2.98 (d, J=4.8 Hz, 3H), 2.72 (s, 3H). MS (M+H)+: 618.

Workup

  1. filtrationafter being filtered through celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. customThe residue was purified by column chromatography (DCM:EtOAc=40:1 to 10:1)

Sources & evidence

ORD record
ord-e0e471285823426cb4c74fe822939770
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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