Potassium Phosphate, Tribasic → HCID 71543514, compound

HRID 1776798Notes

Reaction equation

HRID 1776798 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:52][CH2:51][N:43]3[C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:49]=4[CH:50]=[C:42]3[C:41]=2[N:53]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.CCOC(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].O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:23])=[O:24])[C:18]([C:37]4[CH:38]=[CH:39][C:40]5[O:52][CH2:51][N:43]6[C:44]7[CH:45]=[CH:46][CH:47]=[CH:48][C:49]=7[CH:50]=[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:6][CH:7]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 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 86728227HCID 86728227, compound

Product 1

HCID 71543514HCID 71543514, compoundYield 46.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °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 (502 mg, 1.0 mmol), 2-chloro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (256 mg, 1.0 mmol) and K3PO4 (636 mg, 3.0 mmol) in dioxane:H2O (1.5 mL:0.4 mL) was added Pd2(dba)3 (91 mg, 0.1 mmol) and X-Phos (91 mg, 0.2 mmol) under N2. The mixture was heated to 110° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc and filtered. The filtrate was washed with H2O, brine, dried over Na2SO4. After being concentrated in vacuo, the resulting resulting residue was purified using prep-HPLC to provide the desired product of Compound 1 (275 mg, yield: 46.1%). 1H-NMR (CDCl3, 400 MHz) δ 7.88˜7.94 (m, 3H), 7.61˜7.63 (m, 2H), 7.40 (s, 2H), 7.09˜7.28 (m, 6H), 5.94 (s, 2H), 5.86 (d, J=4.4 Hz, 1H), 3.29 (s, 3H), 2.92 (d, J=4.8 Hz, 3H), 2.65 (s, 3H). MS (M+H)+: 597.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated in vacuo
  6. customthe resulting resulting residue
  7. customwas purified

Sources & evidence

ORD record
ord-c62ca254e640430db97b61e6180d2f5b
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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