Cesium carbonate → 2-(4-fluorophenyl)-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

HRID 1621534Notes

Reaction equation

HRID 1621534 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[C:5]([C:17]2[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([S:24][CH3:25])[N:18]=2)=[CH:4][N:3]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[NH4+].[Cl-].[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=3)[C:5]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([S:24][CH3:25])[N:18]=3)=[CH:4][N:3]=2)=[CH:29][CH:28]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 866470542-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine

Product 1

HCID 665998562-(4-fluorophenyl)-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amineYield 52.5%

Reagents, catalysts & solvents 4

HCID 178478230HCID 178478230, compoundCatalystHCID 962WaterSolventHCID 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (38 mg, 0.101 mmol), 4-fluorobenzeneboronic acid (16.98 mg, 0.121 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (8.26 mg, 10.11 μmol) and cesium carbonate (66 mg, 0.202 mmol) in dioxane (3 mL) and water (0.5 mL) was stirred at 100° C. for 1 h. The mixture was cooled down to room temperature. The reaction mixture was diluted with saturated NH4Cl (5 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as an orange solid. The crude product was purified by silica gel chromatography eluting with 30% EtOAc/hexanes to give 2-(4-fluorophenyl)-N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidin-4-amine (23 mg, 0.053 mmol, 52.2% yield). 1H NMR (300 MHz, CDCl3) δ 11.64 (s, 1H); 9.73 (s, 1H); 8.39-8.50 (m, 3H); 8.11 (dd, J=8.77, 2.48 Hz, 1H); 7.16 (t, J=8.62 Hz, 2H); 6.87 (d, J=8.92 Hz, 1H); 4.00 (s, 3H); 2.67 (d, J=4.38 Hz, 6H). m/z (ESI, +ve ion) 436.1 (M+H)+.

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as an orange solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-250a82baa878486aaf3971c9436274f1
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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