6-Methoxy-3-pyridinylamine → 6-methoxy-N-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)pyridin-3-amine

HRID 1621430Notes

Reaction equation

HRID 1621430 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[N:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:24][O:25][C:26]1[N:31]=[CH:30][C:29]([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:28][CH:27]=1

Participants

5

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 601548206-methoxy-N-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)pyridin-3-amineYield 38.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (190 mg, 606 μmol) and 6-methoxypyridin-3-amine (94.1 mg, 758 μmol) (Aldrich, St. Louis, Mo.) in THF (2.0 mL) was cooled in an ice bath and treated with LiHMDS (3.0 mL, 3.0 mmol)(a 1.0 M in THF solution). A blood-red solution was obtained. The mixture was stirred for 1 h, and then quenched with water (0.1 mL). The mixture was extracted into EtOAc from saturated aqueous NaHCO3, concentrated and purified by flash chromatography on silica (25 to 50% EtOAc/hexane; yellow band from column) to give 6-methoxy-N-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)pyridin-3-amine (96.3 mg, 38.0% yield) as a yellow crystalline solid. 1H NMR (400 MHz, d6-DMSO) δ 12.50 (s, 1H); 9.72 (dd, J=7.82, 1.71 Hz, 1H); 8.87 (s, 1H); 8.53 (d, J=2.69 Hz, 1H); 8.32 (dd, J=4.65, 1.96 Hz, 1H); 8.18 (dd, J=8.93, 2.81 Hz, 1H); 7.01 (dd, J=7.82, 4.65 Hz, 1H); 6.85 (d, J=9.05 Hz, 1H); 5.80-5.89 (m, 1H); 3.97-4.12 (m, 1H); 3.85 (s, 3H); 3.67-3.82 (m, 1H); 2.89 (s, 3H); 2.27-2.38 (m, 1H); 1.93-2.12 (m, 2H); 1.72-1.88 (m, 1H); 1.55-1.70 (m, 2H). m/z (ESI, +ve) 418.1 (M+H)+.

Workup

  1. customA blood-red solution was obtained
  2. customquenched with water (0.1 mL)
  3. extractionThe mixture was extracted into EtOAc from saturated aqueous NaHCO3
  4. concentrationconcentrated
  5. custompurified by flash chromatography on silica (25 to 50% EtOAc/hexane; yellow band from column)

Sources & evidence

ORD record
ord-22a6d1b3d3b949d18d2bba7d2aff0245
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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