Acetic Acid → 3-Cyclopropylmethyl-8-[4-((1-methyl)-ethyl-amino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

HRID 720690Notes

Reaction equation

HRID 720690 reaction equation
[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=4)[NH:10][C:9]=3[C:8](=[O:22])[N:7]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:6]2=[O:31])[CH2:3][CH2:2]1.[CH3:32][C:33]([CH3:35])=O.C([BH3-])#N.[Na+].C(O)(=O)C>O1CCCC1.ClCCl>[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:16]=[CH:17][C:18]([NH:21][CH:33]([CH3:35])[CH3:32])=[CH:19][CH:20]=4)[NH:10][C:9]=3[C:8](=[O:22])[N:7]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:6]2=[O:31])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 180AcetoneHCID 5003444Sodium cyanoborohydrideHCID 218917373-Cyclopropylmethyl-8-[4-aminobenzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

Product 1

HCID 587392683-Cyclopropylmethyl-8-[4-((1-methyl)-ethyl-amino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dioneYield 23.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-cyclopropylmethyl-8-[4-aminobenzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione (0.21 g, 0.50 mmol) in tetrahydrofuran (tetrahydrofuran) (5 mL) was added acetone (36.7 μL, 5.0 mmol) and sodium cyanoborohydride (Aldrich, catalog number 15,615-9) (94.3 mg, 1.5 mmol). Stirred vigorously at ambient temperature and glacial acetic acid (J. T. Baker, catalog number 9508-5) (50 μL, 0.87 mmol) added. After 3 h additional glacial acetic acid (50 μL, 0.87 mmol) was added and the mixture stirred at ambient temperature for an additional 1 h. The reaction mixture was diluted with dichloromethane and washed with 1M aqueous sodium hydroxide (2×), brine, dried (sodium sulfate) and concentrated in vacuo. The residue was purified by chromatography using silica eluted with 1:2 hexanes/ethyl acetate. Concentration of the appropriate fractions gave the product as a colorless solid (0.055 g, 23%). 1H NMR, δH(DMSO-d6, 300 MHz) 13.29 (br s, 1H), 7.30–6.85 (m, 6H), 6.40 (d, J=8.8 Hz, 2H), 5.16 (d, J=8.4 Hz, 1H), 5.04 (s, 2H), 3.78 (s, 2H), 3.42 (sept, J=6.4 Hz, 1H), 1.25–1.10 (m, 1H), 1.01 (d, J=6.2 Hz, 6H) and 0.45–0.30 (m, 4H)

Workup

  1. stirringthe mixture stirred at ambient temperature for an additional 1 h
  2. washwashed with 1M aqueous sodium hydroxide (2×), brine
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography
  6. washeluted with 1:2 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-9addbce7c5894479b10ff3a709ba8ff4
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

Loading…