Pyridine → HCID 11464110, compound

HRID 2181627Notes

Reaction equation

HRID 2181627 reaction equation
[CH2:1]([C:3]1[N:11]([CH:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[C:10]2[C:9](=[O:19])[N:8]([CH3:20])[C:7](=[O:21])[NH:6][C:5]=2[N:4]=1)[CH3:2].[CH3:22][O:23]C1N=C(C)C(B(O)O)=CC=1.[N:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[NH4+].[Cl-].[NH4+].[OH-].[CH2:44](Cl)Cl>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:1]([C:3]1[N:11]([CH:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[C:10]2[C:9](=[O:19])[N:8]([CH3:20])[C:7](=[O:21])[N:6]([C:36]3[C:35]([CH3:44])=[N:34][CH:39]=[CH:38][C:37]=3[O:23][CH3:22])[C:5]=2[N:4]=1)[CH3:2]

Participants

8

Reactant 6

HCID 1049PyridineHCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 27630842-Methyl-6-methoxypyridine-3-boronic acid2×HCID 11150504HCID 11150504, compound

Product 1

HCID 11464110HCID 11464110, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst2×

Procedure

8-ethyl-7-(4-heptyl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione (3.30 g, 11.3 mmol), 6-methoxy-2-methyl-3-pyridineboronic acid (2.84 g, 17.0 mmol), copper (II) acetate (3.07 g, 17 mmol), and 4 A powdered molecular sieves (3.0 g) were combined in a 200 mL round bottom flask. CH2Cl2 (25 mL) and pyridine (1.81 mL, 22.6 mmol) were added and the reaction mixture was stirred at rt for 2 days. Additional 6-methoxy-2-methyl-3-pyridineboronic acid (1.50 g, 8.98 mmol) and copper (II) acetate (2.0 g, 11.0 mmol) was added and the reaction mixture was stirred at rt for an additional 2 days. The mixture was poured into a separatory funnel containing saturated aqueous NH4Cl (100 mL) and conc NH4OH (150 mL). The aqueous layer was extracted with EtOAc (4×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (30% ethyl acetate in hexanes then 75% ethyl acetate/25% hexanes to recover starting material) to furnish 8-ethyl-7-(4-heptyl)-3-(4-methoxy-2-methylpyrid-3-yl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione (1.92 g, 41% yield) and recovered starting material (1.72 g, 52% recovery). The product was isolated as a colorless solid: 87-94° C.; 1H NMR (300 MHz, CDCl3) δ 7.45 (d, J=8.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 1H), 4.17-4.08 (m, 1H), 3.95 (s, 3H), 3.47 (s, 3H), 2.73 (q, J=7.3 Hz, 2H), 2.32-2.23 (m, 1H), 2.25 (s, 3H), 1.98-1.80 (m, 3H), 1.30-1.05 (m, 4H), 1.24 (t, J=7.3 Hz, 3H), 0.94-0.88 (m, 6H); LRMS (APCI) m/e 414.6 [(M+H)+, calcd for C22H32N5O3 414.3].

Workup

  1. stirringthe reaction mixture was stirred at rt for an additional 2 days
  2. additionThe mixture was poured into a separatory funnel
  3. extractionThe aqueous layer was extracted with EtOAc (4×100 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (30% ethyl acetate in hexanes
  9. custom75% ethyl acetate/25% hexanes to recover

Sources & evidence

ORD record
ord-910f54fd98f44748b2a8f1c52c1f4f8b
Source dataset
uspto-grants-2005_05
Patent number
US06894045B2

Reaction notes

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