6-Methoxy-3-pyridinylamine → HCID 66600240, compound

HRID 1811786Notes

Reaction equation

HRID 1811786 reaction equation
F[C:2]1[C:7]([C:8]2[N:16]=[CH:15][N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:31][O:30][C:27]1[N:26]=[CH:25][C:24]([NH:23][C:2]2[C:7]([C:8]3[N:16]=[CH:15][N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][N:12]4[CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 44479178HCID 44479178, compound

Product 1

HCID 66600240HCID 66600240, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (196.6 mg, 657 μmol) and 3-amino-6-methoxypyridine (Aldrich, St. Louis, Mo.) (101.9 mg, 821 μmol) in THF (2.0 mL) was cooled in an ice bath and treated with LiHMDS (3.0 mL, 3.0 mmol). 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 (50% EtOAc/hexane; yellow band from column) to give 6-methoxy-N-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)pyridin-3-amine (190 mg, 71.7% yield) as a yellow crystalline solid. 1H NMR (400 MHz, CDCl3) δ 12.06 (s, 1H); 9.68 (dd, J=7.82, 1.76 Hz, 1H); 8.99 (s, 1H); 8.44 (d, J=2.54 Hz, 1H); 8.28 (dd, J=4.69, 1.76 Hz, 1H) 8.34 (s, 1H); 8.05 (dd, J=8.90, 2.64 Hz, 1H); 6.88 (dd, J=7.82, 4.69 Hz, 1H); 6.77 (d, J=8.80 Hz, 1H); 5.86 (dd, J=10.37, 2.35 Hz, 1H); 4.16-4.25 (m, 1H); 3.95 (s, 3H); 3.82 (s, 1H); 1.98-2.24 (m, 3H); 1.61-1.89 (m, 3H). m/z (ESI, +ve) 404.0 (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 (50% EtOAc/hexane; yellow band from column)

Sources & evidence

ORD record
ord-2591f4a44da746538b83c47155e8367f
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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