HCID 58266306, compound → HCID 58266813, compound

HRID 1506045Notes

Reaction equation

HRID 1506045 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:24])=[N:11][CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)[CH:3]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29](OS(C(F)(F)F)(=O)=O)[CH:30]=[C:31]([O:40][CH3:41])[C:32]=1[CH2:33][N:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>[F-].[K+].C(#N)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:24])=[N:11][CH:12]=[C:13]([C:29]3[CH:30]=[C:31]([O:40][CH3:41])[C:32]([CH2:33][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[C:27]([O:26][CH3:25])[CH:28]=3)[CH:14]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 58266306HCID 58266306, compoundHCID 58266390HCID 58266390, compound

Product 1

HCID 58266813HCID 58266813, compoundYield 100.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of 6′-chloro-2-fluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-[3,4′]bipyridinyl-3′-ylamine (630 mg, 1.80 mmol), trifluoromethanesulfonic acid 3,5-dimethoxy-4-piperidin-1-ylmethylphenyl ester (1.06 g, 1.98 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (147 mg, 0.18 mmol) in 1N aqueous potassium fluoride solution (10 mL) and acetonitrile (8 mL) was heated under microwave irradiation at 100° C. for 30 minutes. The cooled reaction mixture was partitioned between DCM (50 mL) and brine (50 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 20 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a white solid (830 mg, 76%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.52-8.57 (m, 1H), 8.12-8.19 (m, 1H), 7.98 (s, 1H), 7.19 (s, 1H), 6.91 (s, 2H), 4.34 (s, 2H), 4.01 (s, 6H), 2.87-3.64 (ν br m, 4H), 1.63-2.02 (s, 6H).

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between DCM (50 mL) and brine (50 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 20 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-242f0692d52a4d278b65bb6e32a4992a
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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