Hydrochloric Acid → 2-chloro-7H-purine

HRID 2073654Notes

Reaction equation

HRID 2073654 reaction equation
N[C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4](Cl)[N:3]=1.C[Si](C)(C)N[Si](C)(C)C.S([O-])([O-])(=O)=O.[NH4+].[NH4+].[Cl:28]COC(COCC1C=CC=CC=1)COCCCCCCC.C(OCC(O)COCC1C=CC=CC=1)CCCCCC.C=O.Cl>C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:28][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[CH:4][N:3]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 13838HexamethyldisilazaneHCID 53603492-Amino-6-chloropurineHCID 6097028Ammonium SulfateHCID 143916171-(Heptyloxy)-3-(phenylmethoxy)-2-propanolHCID 146965862-(Chloromethoxy)-1-(heptyloxy)-3-(phenylmethoxy)propane

Product 1

HCID 5193142-chloro-7H-purine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-6-chloropurine (Aldrich Chemical Co.) 11.2 g, 0.066 mol) hexamethyldisilazane (160 ml), and ammonium sulfate (1.09 g) is refluxed for 2.5 hours and then cooled, concentrated and pumped to dryness. The residue is dissolved in dry toluene (210 ml) and is treated with Hg(CN)2. The mixture is heated to 80° C. and a solution of 2-(chloromethoxy)-1-(heptyloxy)-3-(phenylmethoxy)propane (prepared from 1-(heptyloxy)-3-(phenylmethoxy)-2-propanol (19 g, 0.068 mol), paraformaldehyde (4 g) and dry HCl (g) in CH2Cl2 (160 ml) as described in the first part of Example 7, in toluene (210 ml) is added to the solution and heated to 80°-85° C. for 2.5 hours. The mixture is cooled, concentrated, and diluted with CH2Cl2 (1.0 L) and is allowed to stand overnight. The CH2Cl2 solution is filtered, washed with 30% KI, 10% potassium carbonate solution and water. The organic layer is dried and concentrated. The residue is chromatographed over silica gel column using a high pressure liquid chromatographic instrument (Waters Prep 500). The column is eluted with ethyl acetate and hexane (1:1) to give the condensation product (i.e., chloropurine drivative) (6.45 g) which is hydrolysed as follows.

Workup

  1. temperatureis refluxed for 2.5 hours
  2. temperaturecooled
  3. concentrationconcentrated
  4. dissolutionThe residue is dissolved in dry toluene (210 ml)
  5. additionis treated with Hg(CN)2
  6. additionis added to the solution
  7. temperatureheated to 80°-85° C. for 2.5 hours
  8. temperatureThe mixture is cooled
  9. concentrationconcentrated
  10. additiondiluted with CH2Cl2 (1.0 L)
  11. filtrationThe CH2Cl2 solution is filtered
  12. washwashed with 30% KI, 10% potassium carbonate solution and water
  13. customThe organic layer is dried
  14. concentrationconcentrated
  15. customThe residue is chromatographed over silica gel column
  16. washThe column is eluted with ethyl acetate and hexane (1:1)

Sources & evidence

ORD record
ord-c03d67002a2145b29c3378c10b8fc086
Source dataset
uspto-grants-1990_04
Patent number
US04918219

Reaction notes

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