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

HRID 1811945Notes

Reaction equation

HRID 1811945 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.[N:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[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]>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([NH:8][C:6]2[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]=[C:2]([C:29]3[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=3)[N:7]=2)=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic 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 66611390N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-2-(pyridin-4-yl)pyrimidin-4-amineYield 26%

Reagents, catalysts & solvents 3

HCID 178478230HCID 178478230, compoundCatalystHCID 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), pyridine-4-boronic acid (14.91 mg, 0.121 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (8.26 mg, 10.11 μmol) and cesium carbonate (39 mg, 0.121 mmol) in dioxane (1 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 (10 mL) and extracted with EtOAc (2×20 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 product as an orange solid. The crude product was purified by silica gel chromatography eluting with 10% MeOH/EtOAc to give N-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-2-(pyridin-4-yl)pyrimidin-4-amine (11 mg, 0.026 mmol, 26.0% yield). 1H NMR (300 MHz, CDCl3) δ 11.69 (s, 1H); 9.78 (s, 1H); 8.62-9.02 (m, 2H); 8.46 (s, 1H); 8.29-8.43 (m, 1H); 8.24 (d, J=4.53 Hz, 1H); 8.04-8.14 (m, 1H); 6.79-6.93 (m, 1H); 5.30 (s, 2H); 4.00 (s, 3H); 2.69 (s, 3H); 2.67 (s, 3H). m/z (ESI, +ve ion) 419.1 (M+H)+.

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. extractionextracted with EtOAc (2×20 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 product as an orange solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-8eab79a67b79420b9b3444a23c81de3e
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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