Triethylamine → 6-(4-Hydroxy-3-methylbutylamino)-9-(tetrahydropyran-2-yl)purine

HRID 2422327Notes

Reaction equation

HRID 2422327 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.ClC1N=CN=C2C=1NC=N2.C(O)(=O)C(O)=O.[OH:33][CH2:34][CH:35]([CH3:39])[CH2:36][CH2:37][NH2:38].C(N(CC)CC)C>C(O)CC>[OH:33][CH2:34][CH:35]([CH3:39])[CH2:36][CH2:37][NH:38][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 53592776-ChloropurineHCID 866321794-Hydroxy-3-methylbutylamine oxalate

Product 1

HCID 533909486-(4-Hydroxy-3-methylbutylamino)-9-(tetrahydropyran-2-yl)purineYield 75%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Procedure

A mixture of 10 mmol (2387 mg) 6-chloro-9-(tetrahydropyran-2-yl)purine (prepared from 10 mmol (1546 mg) of 6-chloropurine), 12 mmol (2318 mg) 4-hydroxy-3-methylbutylamine oxalate, and 5 mL of triethylamine was refluxed in n-propanol for 3 hours and subsequently 24 hrs at laboratory temperature. After removal of the n-propanol by vacuum evaporation, the resulting material was treated with water and partitioned into ethyl acetate. The ethyl acetate phase was evaporated and the residuum subsequently washed with 30 ml of hexane. The solid residue was filtered off and the crude product crystallized from methanol. Yield 75%, white solid. TLC (CHCl3:methanol (4:1) (v:v): single spot; HPLC: purity >98%. 1H-NMR (400 MHz, DMSO): 0.88d (3H, J=6.6 Hz); 1.34m (1H); 1.56m (3H); 1.70m (1H); 1.71m (1H); 1.93m (2H); 1.94m (1H); 2.26m (1H); 3.25m (1H); 3.52bs (2H); 3.67m (1H); 4.0d (1H, J=11.3 Hz); 4.42t (1H, J=5.1 Hz); 5.61d (1H, J=10.6 Hz); 7.70bs (1H); 8.20s (1H); 8.30s (1H). MS (ES): [M+H]+=306 (100).

Workup

  1. customAfter removal of the n-propanol
  2. customby vacuum evaporation
  3. additionthe resulting material was treated with water
  4. custompartitioned into ethyl acetate
  5. customThe ethyl acetate phase was evaporated
  6. washthe residuum subsequently washed with 30 ml of hexane
  7. filtrationThe solid residue was filtered off
  8. customthe crude product crystallized from methanol
  9. custom8.20s (1H)
  10. custom8.30s (1H)

Sources & evidence

ORD record
ord-7fd339a20e9c4d32b125f051e3aa3885
Source dataset
uspto-grants-2011_06
Patent number
US07960397B2

Reaction notes

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