Cesium fluoride → N4-(6-methoxypyridin-3-yl)-N2,N2-dimethyl-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamine

HRID 1811937Notes

Reaction equation

HRID 1811937 reaction equation
I[C:2]1[C:3]([NH:11][C:12]2[CH:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)=[N:4][C:5]([N:8]([CH3:10])[CH3:9])=[N:6][CH:7]=1.[CH3:20][C:21]1[N:26]=[C:25]([S:27][CH3:28])[N:24]=[C:23]([Sn](CCCC)(CCCC)CCCC)[N:22]=1.[F-].[Cs+].O1CCOCC1>O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][O:18][C:15]1[N:14]=[CH:13][C:12]([NH:11][C:3]2[C:2]([C:23]3[N:22]=[C:21]([CH3:20])[N:26]=[C:25]([S:27][CH3:28])[N:24]=3)=[CH:7][N:6]=[C:5]([N:8]([CH3:10])[CH3:9])[N:4]=2)=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 666004095-iodo-N4-(6-methoxypyridin-3-yl)-N2,N2-dimethylpyrimidine-2,4-diamine

Product 1

HCID 66610492N4-(6-methoxypyridin-3-yl)-N2,N2-dimethyl-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamineYield 31.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A glass microwave reaction vessel was charged with 5-iodo-N4-(6-methoxypyridin-3-yl)-N2,N2-dimethylpyrimidine-2,4-diamine (98 mg, 0.264 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (114 mg, 0.264 mmol), cesium fluoride (80 mg, 0.528 mmol), copper(I) iodide (10 mg, 0.053 mmol), tetrakis(triphenylphosphine)palladium(0) (30.5 mg, 0.026 mmol) and dioxane (2 mL). The reaction mixture was stirred and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 30 min. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 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 60% EtOAc/hexanes to give N4-(6-methoxypyridin-3-yl)-N2,N2-dimethyl-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamine (32 mg, 0.083 mmol, 31.5% yield). 1H NMR (300 MHz, CDCl3) δ 11.66 (s, 1H); 9.43 (s, 1H); 8.42 (s, 1H); 8.05 (dd, J=8.70, 2.27 Hz, 1H); 6.77 (d, J=8.92 Hz, 1H); 3.95 (s, 3H); 3.25 (s, 6H); 2.59 (s, 3H); 2.57 (s, 3H). m/z (ESI, +ve ion) 385.1 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (10 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 60% EtOAc/hexanes

Sources & evidence

ORD record
ord-c4bbd9d803c44204a92f77b269f821a4
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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