Acetyl chloride → HCID 87573287, compound

HRID 2264871Notes

Reaction equation

HRID 2264871 reaction equation
C(O[C@@H]1[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1[N:19]1[CH:27]=[N:26][C:25]2[C:20]1=[N:21][C:22]([Cl:29])=[N:23][C:24]=2Cl)(=O)C.[C:30]1([CH:36]([CH3:43])[CH2:37][C:38]2[NH:39][CH:40]=[CH:41][N:42]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(Cl)(C)=O>CC#N.CC(O)=O>[Cl:29][C:22]1[N:21]=[C:20]2[C:25]([NH:26][CH:27]=[N:19]2)=[C:24]([N:39]2[CH:40]=[CH:41][N:42]=[C:38]2[CH2:37][CH:36]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH3:43])[N:23]=1

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 68780556HCID 68780556, compound2×

Product 1

HCID 87573287HCID 87573287, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloropurine (0.98 g, 2.19 mmol) and 2-(2-phenylpropyl)imidazole (4.07 g, 21.9 mmol) in CH3CN (20 mL) was stirred at 65° C. for 17 h (reaction complete, TLC). Volatiles were evaporated in vacuo, and the residue was chromatographed (MeOH/CH2Cl2, 1:90) to give a mixture of diastereomers (quantitative, contaminated with 2-(2-phenylpropyl)imidazole). The mixture was dissolved in HOAc (91 mL), and to the solution was added AcCl (0.92 mL, 1.00 g, 12.8 mmol). The mixture was stirred at 65° C. for 25.5 h in a sealed flask (reaction complete, TLC). Volatiles were evaporated in vacuo, and the residue was dissolved in 0.1 N NaOH/H2O (300 mL) and CHCl3 (150 mL). The mixture was stirred for 2 h, and then neutralized with CO2. The organic phase was separated, and the aqueous phase was extracted with CH2Cl2. The combined organic phase was dried (Na2SO4) and concentrated to dryness. The residue was washed (H2O), suspended in EtOH, and filtered to give 2-chloro-6-[2-(2-phenylpropyl)imidazol-1-yl]purine (0.46 g, 62%) of material. The mother liquor was evaporated to dryness, and the residue was chromatographed (MeOH/CH2Cl2, 1:30→1:12) to give a solid, which was washed (H2O) to give the second crop (0.18 g, 86% total). The combined solids were dissolved in 0.1 N NaOH/H2O (300 mL). Precipitation with CO2 gave 2-chloro-6-[2-(2-phenylpropyl)imidazol-1-yl]purine as an enantiomeric mixture (0.59 g, 80%): mp 258.5-259° C.; UV (MeOH) max 254, 289 nm (∈ 12 000, 4100), min 240, 256 nm (F 3600, 4100); 1H NMR (500 MHz, DMSO-d6) δ 14.00 (s, 1H), 8.68 (s, 1H), 8.35 (s, 1H), 7.13-7.14 (m, 4H), 7.07 (d, J=1.9 Hz, 1H), 7.00-7.04 (m, 1H), 3.58 (dd, J=14.4, 6.7 Hz, 1H), 3.43 (dd, J=14.2, 7.7 Hz, 1H), 3.30 (sext, J=7.0 Hz, 1H), 1.23 (1.22) (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 156.4, 150.9, 147.9, 146.4, 145.8, 145.7, 128.2, 127.9, 126.6, 125.7, 121.7, 120.5, 38.3, 37.7, 21.0; HRMS m/z 361.0935 (MNa+[C17H15ClN6Na]=361.0944). Anal. Calcd for C17H15ClN6: C, 60.27; H, 4.46; N, 24.81. Found: C, 60.12; H, 4.60; N, 24.66.

Workup

  1. custom(reaction complete, TLC)
  2. customVolatiles were evaporated in vacuo
  3. customthe residue was chromatographed (MeOH/CH2Cl2, 1:90)
  4. customto give
  5. stirringThe mixture was stirred at 65° C. for 25.5 h in a sealed flask
  6. custom(reaction complete, TLC)
  7. customVolatiles were evaporated in vacuo
  8. dissolutionthe residue was dissolved in 0.1 N NaOH/H2O (300 mL)
  9. stirringThe mixture was stirred for 2 h
  10. customThe organic phase was separated
  11. extractionthe aqueous phase was extracted with CH2Cl2
  12. dry with materialThe combined organic phase was dried (Na2SO4)
  13. concentrationconcentrated to dryness
  14. washThe residue was washed (H2O)
  15. filtrationfiltered

Sources & evidence

ORD record
ord-40684fefb7ad4a39922a6e79008441b3
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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