2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 89434880, compound

HRID 1776926Notes

Reaction equation

HRID 1776926 reaction equation
[Cl:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]([C:12]2[C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][C:15]3[C:16]([C:26]([NH:28][CH3:29])=[O:27])=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[O:18][C:14]=3[CH:13]=2)[S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl[C:44]1[CH:45]=[CH:46][C:47]2[O:60][CH2:59][N:50]3[C:51]4[CH:52]=[CH:53][CH:54]=[C:55]([F:58])[C:56]=4[CH:57]=[C:49]3[C:48]=2[N:61]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[Cl:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]([C:12]2[C:31]([C:44]3[CH:45]=[CH:46][C:47]4[O:60][CH2:59][N:50]5[C:51]6[CH:52]=[CH:53][CH:54]=[C:55]([F:58])[C:56]=6[CH:57]=[C:49]5[C:48]=4[N:61]=3)=[CH:30][C:15]3[C:16]([C:26]([NH:28][CH3:29])=[O:27])=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[O:18][C:14]=3[CH:13]=2)[S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71295494HCID 71295494, compoundHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Product 1

HCID 89434880HCID 89434880, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(N-(4-chlorobenzyl)methylsulfonamido)-2-(4-fluorophenyl)-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (0.15 g, 0.25 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (0.09 g, 0.33 mmol) and K3PO4.3H2O (0.15 g, 0.56 mmol) in dioxane/H2O (6 mL/12 drops) was added Pd2(dba)3 (12 mg, 0.013 mmol) and X-Phos (12 mg, 0.026 mmol) under N2. The mixture was stirred at 100° C. under reflux for 2 hours. Then it was filtered and extracted with EtOAc. The combined organic phases was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using flash gel chromatography (petroleum ether:EtOAc=2:1) to provide 6-(N-(4-chlorobenzyl)methylsulfonamido)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide. 1H-NMR (CDCl3, 400 MHz) δ 7.90 (s, 1H), 7.82˜7.86 (m, 2H), 7.39 (s, 2H), 7.04˜7.19 (m, 10H), 6.76˜6.80 (m, 1H), 5.95 (s, 2H), 5.86 (s, 1H), 4.66˜4.78 (m, 2H), 2.89 (d, J=4.0 Hz, 3H), 2.74 (s, 3H). MS (M+H)+: 725.

Workup

  1. temperatureunder reflux for 2 hours
  2. filtrationThen it was filtered
  3. extractionextracted with EtOAc
  4. washThe combined organic phases was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-bd37d7b58bb347aca4b06ca12ec6d47b
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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