Hydrochloric Acid → 6-methoxy-N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)pyridin-3-amine

HRID 1621491Notes

Reaction equation

HRID 1621491 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[N:16]=[C:15]([CH3:17])[N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][N:12]2C1CCCCO1.[NH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[N:29][CH:30]=1.Cl>C(O)C.C([O-])(O)=O.[Na+]>[CH3:32][O:31][C:28]1[N:29]=[CH:30][C:25]([NH:24][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][NH:12]3)=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 811216-Methoxy-3-pyridinylamineHCID 666000086-(4-chloropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 1784921376-methoxy-N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)pyridin-3-amineYield 58%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
160 °C

Procedure

A glass microwave reaction vessel was charged with 6-(4-chloropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (36 mg, 0.109 mmol) and 5-amino-2-methoxypyridine (27.1 mg, 0.218 mmol, Aldrich) in ethanol (1 mL) and a drop of 5N HCl. The reaction mixture was stirred and heated in a Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 160° C. for 30 min. The reaction mixture was diluted with NaHCO3 (5 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (3 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a yellow solid. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column eluting with 10% MeOH/CH2Cl2 to provide 6-methoxy-N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)pyridin-3-amine (21 mg, 58% yield) as a yellow solid. 1H NMR (300 MHz, CD3OD) δ 9.98 (s, 1H); 8.42 (s, 1H); 8.07-8.24 (m, 2H); 7.72 (d, J=8.92 Hz, 1H); 6.85-7.00 (m, 2H); 3.96 (s, 3H); 2.83 (s, 3H). m/z (ESI, +ve ion) 334 (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 (3 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow solid
  9. custompurified by chromatography through a silica gel column
  10. washeluting with 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-de218fc701d24797b957697a63787c6b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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