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

HRID 1811950Notes

Reaction equation

HRID 1811950 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[C:10](I)=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:23][C:24]1[N:29]=[C:28]([S:30][CH3:31])[N:27]=[C:26]([Sn](CCCC)(CCCC)CCCC)[N:25]=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>[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[C:10]([C:26]3[N:25]=[C:24]([CH3:23])[N:29]=[C:28]([S:30][CH3:31])[N:27]=3)=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 601547172-Methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazineHCID 66600610N2-cyclopentyl-5-iodo-N4-(6-methoxypyridin-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 66611563N2-cyclopentyl-N4-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamineYield 34.7%

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 N2-cyclopentyl-5-iodo-N4-(6-methoxypyridin-3-yl)pyrimidine-2,4-diamine (145 mg, 0.353 mmol), 2-methyl-4-(methylthio)-6-(tributylstannyl)-1,3,5-triazine (152 mg, 0.353 mmol), copper(I) iodide (14 mg, 0.071 mmol), cesium fluoride (107 mg, 0.705 mmol), tetrakis(triphenylphosphine)palladium(0) (40.7 mg, 0.035 mmol) and dioxane (3 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 20 min. The reaction mixture was diluted with water (10 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 a black solid. The crude product was purified by silica gel chromatography eluting with 50% EtOAc/hexanes to give N2-cyclopentyl-N4-(6-methoxypyridin-3-yl)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyrimidine-2,4-diamine (52 mg, 0.122 mmol, 34.7% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ 11.46-11.87 (m, 1H); 9.15-9.62 (m, 1H); 8.26-8.63 (m, 1H); 7.84-8.26 (m, 1H); 6.77 (d, J=8.77 Hz, 1H); 5.11-5.52 (m, 1H); 4.12-4.56 (m, 1H); 3.95 (s, 3H); 2.59 (d, J=6.87 Hz, 6H); 1.87-2.21 (m, 2H); 1.56-1.87 (m, 4H). m/z (ESI, +ve ion) 425.1 (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 (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a black solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-28c55fe5a8e7408199ac5a5a3e114b41
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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