Ethanol → 5-iodo-N-(6-methoxypyridin-3-yl)-2-morpholinopyrimidin-4-amine

HRID 1621520Notes

Reaction equation

HRID 1621520 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.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(O)C>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]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 8083MorpholineHCID 866470532-chloro-5-iodo-N-(6-methoxypyridin-3-yl)pyrimidin-4-amine

Product 1

HCID 666003165-iodo-N-(6-methoxypyridin-3-yl)-2-morpholinopyrimidin-4-amineYield 89%

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 (160 mg, 0.441 mmol), morpholine (0.077 mL, 0.883 mmol) and ethanol (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 (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as an off-white solid. The crude product was purified by silica gel chromatography eluting with 50% EtOAc/hexanes to give 5-iodo-N-(6-methoxypyridin-3-yl)-2-morpholinopyrimidin-4-amine (162 mg, 0.392 mmol, 89% yield). 1H NMR (300 MHz, CDCl3) δ 8.26 (d, J=1.90 Hz, 1H); 8.20 (s, 1H); 7.72 (dd, J=8.77, 2.34 Hz, 1H); 6.75 (d, J=8.92 Hz, 1H); 6.67 (s, 1H); 3.95 (s, 3H); 3.68 (d, J=5.26 Hz, 8H). m/z (ESI, +ve ion) 414.0 (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 off-white solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-55290bddf5af4812a6c258702151b726
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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