Water → HCID 86716131, compound

HRID 627560Notes

Reaction equation

HRID 627560 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21](Cl)[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]3[Cl:33])([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[OH:9])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)O1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:33][C:19]1[C:18]2[C:23](=[CH:24][CH:25]=[C:16]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[OH:9])[CH:17]=2)[N:22]=[C:21]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)[C:20]=1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 74222811HCID 74222811, compound

Product 1

HCID 86716131HCID 86716131, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (4-chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(pyridin-3-yl)methanol (75 mg, 0.15 mmol, Example 17), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (37 mg, 0.18 mmol), PdCl2(dppf) (11 mg, 0.015 mmol) and K2CO3 (42 mg, 0.30 mmol) in 10 mL of dioxane was combined with 2 mL of water and heated to 70° C. After 3 hours, the reaction mixture was cooled to room temperature, diluted with EtOAc, and washed with water. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified on an ISCO using 0-10% methanol in ethyl acetate and lyophilized to give the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ=8.60 (s, 1H), 8.55 (d, J=4.0 Hz, 1H), 8.45 (d, J=3.5 Hz, 1H), 8.27-8.34 (m, 2H), 8.15 (d, J=8.6 Hz, 1H), 7.73 (dd, J=8.6, 2.0 Hz, 2H), 7.58 (d, J=7.6 Hz, 1H), 7.28-7.36 (m, 8H), 7.08-7.16 (m, 3H); MS m/e 534.8 [M+H]+.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on an ISCO

Sources & evidence

ORD record
ord-e635dcc392104d528fac0c267f342e05
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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