Methanol → N-(5-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine

HRID 1621659Notes

Reaction equation

HRID 1621659 reaction equation
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([NH2:32])[CH:29]=[N:30][CH:31]=1.C[Si](N[Si](C)(C)C)(C)C.[Li].CO>C1COCC1.C(Cl)Cl>[CH3:24][O:25][C:26]1[CH:27]=[C:28]([NH:32][C:2]2[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][N:12]4[CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:29]=[N:30][CH:31]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 127035955-Methoxypyridin-3-ylamineHCID 57426343Lithium bis(trimethylsilyl)amideHCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 66600712N-(5-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amineYield 45.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Argon was bubbled for 2 min through a glass microwave reaction vessel containing 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (100 mg, 0.319 mmol) and 5-methoxypyridin-3-amine (47.5 mg, 0.383 mmol, Astatech, Inc, Bristol, Pa.) in THF (5 mL), and the tube was sealed. The reaction mixture was cooled to 0° C. and lithium bis(trimethylsilyl)amine (1 N in THF, 1 mL, 0.957 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was quenched with saturated NH4Cl and extracted with EtOAc (3×).The combined organic extracts were washed with satd. NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g) eluting with a gradient of 2% to 5% 2 M NH3.MeOH in DCM to give N-(5-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (60 mg, 0.144 mmol, 45.0% yield) as an orange solid. m/z (ESI, +ve ion) 418 (M+H)+.

Workup

  1. customArgon was bubbled for 2 min through a glass microwave reaction vessel
  2. customthe tube was sealed
  3. temperaturewarmed to room temperature
  4. customThe mixture was quenched with saturated NH4Cl
  5. extractionextracted with EtOAc (3×).The combined organic extracts
  6. washwere washed with satd
  7. dry with materialNaCl and dried over Na2SO4
  8. filtrationThe solution was filtered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g)
  11. washeluting with a gradient of 2% to 5% 2 M NH3

Sources & evidence

ORD record
ord-10cdb6fac2484f2088dc4e941b0703f4
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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