Methanol → 5-iodo-2-methoxy-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

HRID 1811930Notes

Reaction equation

HRID 1811930 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]([I:17])=[CH:4][N:3]=1.[CH3:18][O-:19].[Na+].CO>O>[I:17][C:5]1[C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:7][C:2]([O:19][CH3:18])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 866470532-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

Product 1

HCID 666002025-iodo-2-methoxy-N-(6-methoxypyridin-3-yl)pyrimidin-4-amineYield 91%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A glass microwave reaction vessel was charged with 2-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (181 mg, 0.499 mmol), sodium methoxide (0.5 M solution in methanol, 0.043 mL, 0.749 mmol) and methanol (1 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 15 min. The reaction mixture was diluted with water (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 material as a white solid. The crude product was purified by silica gel chromatography eluting with 50% EtOAc/hexanes to give 5-iodo-2-methoxy-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine (162 mg, 0.452 mmol, 91% yield). 1H NMR (300 MHz, CDCl3) δ 8.35 (s, 1H); 8.26 (d, J=2.05 Hz, 1H); 7.83 (dd, J=8.84, 2.56 Hz, 1H); 6.87 (s, 1H); 6.78 (d, J=8.77 Hz, 1H); 3.94 (s, 3H); 3.89 (s, 3H). m/z (ESI, +ve ion) 359.0 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  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 material as a white solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-90b4e02dae304fdf9efbd03662d39959
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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