2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 1426960-33-9

HRID 1776945Notes

Reaction equation

HRID 1776945 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](B4OC(C)(C)C(C)(C)O4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Cl[C:37]1[CH:38]=[CH:39][C:40]2[O:53][CH2:52][N:43]3[C:44]4[CH:45]=[CH:46][CH:47]=[C:48]([F:51])[C:49]=4[CH:50]=[C:42]3[C:41]=2[N:54]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.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]>[F:51][C:48]1[C:49]2[CH:50]=[C:42]3[C:41]4[N:54]=[C:37]([C:18]5[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:23])=[O:24])=[CH:20][C:10]6[O:9][C:8]([C:5]7[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=7)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=6[CH:17]=5)[CH:38]=[CH:39][C:40]=4[O:53][CH2:52][N:43]3[C:44]=2[CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Product 1

HCID 715091141426960-33-9Yield 49.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.199 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (56 mg, 0.199 mmol) and K3PO4.3H2O (159 mg, 0.597 mmol) in dioxane/H2O (0.8 mL/0.2 mL) was added Pd2(dba)3 (9 mg, 0.01 mmol) and X-Phos (9 mg, 0.02 mmol) under N2. The mixture was heated at 80° C. for 1 hour. The mixture was then diluted with water (30 mL) and extracted with EtOAc (15 mL×3). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether/EtOAc=1:1.5) to provide the pure product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (60 mg, 48.8%). 1H-NMR (CDCl3, 400 MHz) δ: 7.99 (s, 1H), 7.93˜7.96 (m, 2H), 7.65 (s, 1H), 7.45˜7.50 (m, 2H), 7.17˜7.21 (m, 4H), 7.10 (d, J=8.0 Hz, 1H), 6.81˜6.85 (m, 1H), 5.98 (s, 3H), 3.35 (s, 3H), 2.98 (d, J=4.8 Hz, 3H), 2.72 (s, 3H). MS (M+H)+: 615.

Workup

  1. extractionextracted with EtOAc (15 mL×3)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

Sources & evidence

ORD record
ord-75a460cd7a4140b4ac97fe14ce7fa428
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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