Potassium Carbonate → HCID 72551161, compound

HRID 1057025Notes

Reaction equation

HRID 1057025 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][N:11]=2)[CH:3]=1.[O:18]1[CH2:23][CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH2:20][CH2:19]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[O:18]1[CH2:19][CH:20]=[C:21]([C:2]2[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]3[CH:15]=[C:14]([CH:13]=[CH:12][N:11]=3)[C:16]#[N:17])[CH:3]=2)[CH2:22][CH2:23]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol ester2×HCID 90015432HCID 90015432, compound

Product 1

HCID 72551161HCID 72551161, compoundYield 61.3%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 178477754HCID 178477754, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

Into a vial was weighed 2-[(4-chloro-6-methyl-2-pyridyl)amino]pyridine-4-carbonitrile (282 mg, 1.15 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (85.1 mg, 10 mol %), 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester (374 mg, 1.73 mmol) and potassium carbonate (478 mg, 3.46 mmol). After purging with nitrogen, the vial was charged with degassed 1,4-dioxane (2.3 mL) and degassed water (1 mL) and the reaction mixture was stirred at 80° C. overnight. The reaction was barely progressing at all as determined by RPLC and so bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (˜50 mg) and more 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester (374 mg, 1.73 mmol) was added and the reaction temperature was increased to 100° C. and stirred overnight again. After cooling to rt and filtration through Celite, rinsing with CH2Cl2, the mother liquor was washed with brine and dried over MgSO4. Purification by flash column chromatography (100:0-95:5 CH2Cl2/MeOH) afforded 2-((4-(3,6-dihydro-2H-pyran-4-yl)-6-methylpyridin-2-yl)amino)isonicotinonitrile as a red solid (206 mg, 61%); 1H NMR (400 MHz, DMSO) δ 10.07 (br s, 1H), 8.44 (d, J=5.0 Hz, 1H), 8.21 (s, 1H), 7.51 (s, 1H), 7.23 (d, J=5.0 Hz, 1H), 6.93 (s, 1H), 6.45 (s, 1H), 4.25 (s, 2H), 3.83 (m, 2H), 2.43 (s, 3H), 2.41 (m, 2H); ESI-LRMS m/z [M+1]+=293.

Workup

  1. customAfter purging with nitrogen
  2. additionthe vial was charged with degassed 1,4-dioxane (2.3 mL)
  3. customdegassed water (1 mL)
  4. additionwas added
  5. temperaturethe reaction temperature was increased to 100° C.
  6. stirringstirred overnight again
  7. temperatureAfter cooling to rt
  8. filtrationfiltration through Celite
  9. washrinsing with CH2Cl2
  10. washthe mother liquor was washed with brine
  11. dry with materialdried over MgSO4
  12. customPurification by flash column chromatography (100:0-95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-ea78dd21aec34e3d9868ea6e973a53e6
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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