Potassium Phosphate, Tribasic → HCID 71543495, compound

HRID 1776832Notes

Reaction equation

HRID 1776832 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]=[CH:48][C:49]=4[C:50]([F:51])=[C:42]3[C:41]=2[N:54]=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.O.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]>[F:51][C:50]1[C:49]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[N:43]2[CH2:52][O:53][C:40]3[CH:39]=[CH:38][C:37]([C:18]4[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][C:10]5[O:9][C:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=5[CH:17]=4)=[N:54][C:41]=3[C:42]=12

Participants

8

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 86728241HCID 86728241, compound

Product 1

HCID 71543495HCID 71543495, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 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 (110 mg, 0.22 mmol), 2-chloro-12-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (60 mg, 0.220 mmol) and K3PO4 (176 mg, 0.66 mmol) in dioxane/H2O (0.8 mL/0.2 mL) was added Pd2(dba)3 (10 mg, 0.01 mmol) and X-Phos (10 mg, 0.02 mmol) under N2. The mixture was heated to 80° C. and then stirred for 1 hour. The reaction mixture was cooled to RT, diluted with EtOAc and filtered. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the resulting residue was purified using prep-TLC (petroleum ether:EtOAc=1:1) to provide the desired product of compound 58 (60 mg, yield: 44.4%). 1H-NMR (CDCl3, 400 MHz) δ 7.94˜8.00 (m, 3H), 7.66˜7.68 (m, 2H), 7.46 (s, 2H), 7.29˜7.35 (m, 2H), 7.19 (t, J=8.4 Hz, 3H), 6.02 (s, 1H), 5.91 (s, 2H), 3.39 (s, 3H), 2.98 (d, J=4.8 Hz, 3H), 2.70 (s, 3H). MS (M+H)+: 615.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe resulting residue was purified

Sources & evidence

ORD record
ord-0e28db1df8df4f69bb34d0015bf542c8
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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