Potassium Carbonate → HCID 118005536, compound

HRID 1478516Notes

Reaction equation

HRID 1478516 reaction equation
C(O[C:9]1[C:10]([O:38][CH3:39])=[N:11][C:12]2[C:17]([C:18]=1[Cl:19])=[CH:16][C:15]([C:20]([C:32]1[N:36]([CH3:37])[CH:35]=[N:34][CH:33]=1)([C:22]1[CH:23]=[N:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=1)[OH:21])=[CH:14][CH:13]=2)C1C=CC=CC=1.[CH3:40][S:41]([C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1)(=[O:43])=[O:42].C([O-])([O-])=O.[K+].[K+]>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:19][C:18]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:20]([C:32]3[N:36]([CH3:37])[CH:35]=[N:34][CH:33]=3)([C:22]3[CH:23]=[N:24][C:25]([C:28]([F:30])([F:31])[F:29])=[CH:26][CH:27]=3)[OH:21])[CH:16]=2)[N:11]=[C:10]([O:38][CH3:39])[C:9]=1[C:47]1[CH:48]=[CH:49][C:44]([S:41]([CH3:40])(=[O:43])=[O:42])=[CH:45][CH:46]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 118005574HCID 118005574, compound2×

Product 1

HCID 118005536HCID 118005536, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
65 °C

Procedure

A mixture of 4-chloro-6-(hydroxy(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methyl)-2-methoxyquinolin-3-yl trifluoromethanesulfonate (70 mg, 0.12 mmol, Intermediate 11: step g), (4-(methylsulfonyl)phenyl)boronic acid (35 mg, 0.18 mmol), PdCl2(dppf) (9 mg, 0.012 mmol) and K2CO3 (16 mg, 0.12 mmol) was sparged with nitrogen three times. To this mixture was added 1,4-dioxane (2 mL) and water (0.3 mL) and the suspension purged with nitrogen. The resulting solution was heated to 65° C. for 15 hours. The reaction was allowed to cool to room temperature and concentrated to dryness. The residue was dissolved in DMSO, filtered and purified by reverse-phase HPLC (acetonitrile/water+TFA). The acidic fractions were neutralized by diluting with EtOAc and washing with saturated aqueous NaHCO3 followed by water. The organics were dried (MgSO4), filtered and concentrated to dryness to provide the title compound. 1H NMR (400 MHz, CD3OD) δ 8.79-8.76 (m, 1H), 8.24-8.20 (m, 1H), 8.08-8.05 (m, 2H), 8.05-8.01 (m, 1H), 7.96-7.93 (m, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.76-7.72 (m, 2H), 7.65-7.62 (m, 2H), 6.35 (s, 1H), 4.00 (s, 3H), 3.49 (s, 3H), 3.20 (s, 3H); MS (ESI): mass calcd. for C28H22ClF3N4O4S, 602.1; m/z found, 603.2 [M+H]+.

Workup

  1. customwas sparged with nitrogen three times
  2. additionTo this mixture was added 1,4-dioxane (2 mL) and water (0.3 mL)
  3. customthe suspension purged with nitrogen
  4. temperatureto cool to room temperature
  5. concentrationconcentrated to dryness
  6. dissolutionThe residue was dissolved in DMSO
  7. filtrationfiltered
  8. custompurified by reverse-phase HPLC (acetonitrile/water+TFA)
  9. additionby diluting with EtOAc
  10. washwashing with saturated aqueous NaHCO3
  11. dry with materialThe organics were dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-02dbdeb819b04fa68c257c18e60003c6
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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