Potassium Phosphate, Tribasic → HCID 59457676, compound

HRID 2193771Notes

Reaction equation

HRID 2193771 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=3)[S:10][C:3]=12.[F:17][C:18]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:19]=1[NH2:20].C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:17][C:18]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:19]=1[NH:20][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=3)[S:10][C:3]=12

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 1012542-Fluoro-4-nitroanilineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 594245247-Chloro-2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridine

Product 1

HCID 59457676HCID 59457676, compoundYield 50.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A stirred suspension of 10 (500 mg, 2.00 mmol), 337 (406 mg, 2.60 mmol), Pd2(dba)3 (73 mg, 0.08 mmol), (2-biphenyl)dicyclohexylphosphine (56 mg, 0.16 mmol), and K3PO4 (638 mg, 3.00 mmol) in toluene (20 ml) was degased for 15 min with nitrogen at room temperature, and then heated in a sealed flask at 110° C. for 22 hrs (J. P. Wolfe, H. Tomori, J. P. Sadighi. J. Yin. S. L. Buchwald J. Org. Chem. 2000, 65, 1158-1174). After cooling to room temperature the reaction mixture was filtered, rinsed with toluene, concentrated and adsorbed on silica gel. The crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 10/90) and precipitated in AcOEt/hexanes to afford title compound 338 (370 mg, 50% yield) as a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.57 (bs, 1H), 8.45 (d, 5.1 Hz, 1H), 8.22 (dd, J=11.3, 2.5 Hz, 1H), 8.06 (dd. J=8.9, 2.3 Hz, 1H), 7.83 (d, I=1.2 Hz, 1H), 7.70 (d, J=1.2 Hz, 1H), 7.63 (s, 1H), 7.24 (t, J=8.7 Hz, 1H), 6.94 (bd, J=4.7 Hz, 1H), 3.71 (s, 3H). MS (m/z): 370.0 (M+H)+.

Workup

  1. customwas degased for 15 min with nitrogen at room temperature
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. filtrationwas filtered
  4. washrinsed with toluene
  5. concentrationconcentrated
  6. customThe crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 10/90)
  7. customprecipitated in AcOEt/hexanes

Sources & evidence

ORD record
ord-cc0cd04a63b9406a8232efe44d5969b1
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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