2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 71543464, compound

HRID 1776820Notes

Reaction equation

HRID 1776820 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:45][CH2:44][N:43]3[C:46]4[N:52]=[CH:51][CH:50]=[CH:49][C:47]=4[CH:48]=[C:42]3[C:41]=2[N:53]=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]>[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]([C:37]4[CH:38]=[CH:39][C:40]5[O:45][CH2:44][N:43]6[C:46]7[N:52]=[CH:51][CH:50]=[CH:49][C:47]=7[CH:48]=[C:42]6[C:41]=5[N:53]=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1

Participants

6

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 86728234HCID 86728234, compound

Product 1

HCID 71543464HCID 71543464, compoundYield 62.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

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 (40 mg, 0.08 mmol), 2-chloro-6H-pyrido[2,3-e]pyrido[3′,2′:4,5]pyrrolo[1,2-c][1,3]oxazine (27 mg, 0.10 mmol) and K3PO4.3H2O (64 mg, 0.24 mmol) in 1,4-dioxane/water (1.5 mL/0.2 mL), Pd2(dba)3 (5 mg), X-Phos (10 mg) were added under N2 protection. After stirred overnight at 80° C., the reaction mixture was concentrated in vacuo, suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (dichloromethane:MeOH=20:1) to provide the product of Compound 48 (30 mg, yield: 48%). 1H-NMR (CDCl3, 400 MHz) δ 8.34˜8.37 (m, 1H), 8.04 (s, 1H), 7.93˜8.00 (m, 3H), 7.68 (s, 1H), 7.48˜7.56 (m, 2H), 7.17˜7.24 (m, 2H), 7.10˜7.16 (m, 2H), 6.22 (s, 2H), 5.96 (br s, 1H), 3.53 (s, 3H), 3.00 (d, J=4.8 Hz, 3H), 2.76 (s, 3H). MS (M+H)+: 598.

Workup

  1. additionwere added under N2 protection
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. extractionextracted with EtOAc
  4. washThe organic layer 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-04d69aa3e8b04ee09fc14ef1d35e7860
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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