Reaction #44901

ord-1907f8719254478fb587098d77c72465

Reaction equation

Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine
Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Adenosine
CCn1nnc([C@@H]2O[C@@H](n3cnc4c(N[C@H]5CC[C@H](Nc6nc(Cl)nc7c6ncn7[C@@H]6O[C@@H](c7nnn(CC)n7)[C@H](CC(=O)[O-])[C@H]6CC(=O)[O-])CC5)nc(Cl)nc43)[C@H](CC(=O)[O-])[C@H]2CC(=O)[O-])n1
Intermediate 1
CCn1nnc([C@@H]2O[C@@H](n3cnc4c(N[C@H]5CC[C@H](Nc6nc(Cl)nc7c6ncn7[C@@H]6O[C@@H](c7nnn(CC)n7)[C@H](CC(=O)[O-])[C@H]6CC(=O)[O-])CC5)nc(Cl)nc43)[C@H](CC(=O)[O-])[C@H]2CC(=O)[O-])n1
Trans-1,4-cyclohexanediylbis[imino(2-chloro-9H-purine-6,9-diyl)(2R,3R,4R,5R)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-2,3,4-triyl]tetraacetate
N[C@H]1CC[C@H](N)CC1
trans-1,4-diaminocyclohexane
CCN(C(C)C)C(C)C
di-iso-propylethylamine
→
Clc1nc(N[C@H]2CC[C@H](Nc3nc(Cl)nc4c3ncn4C3CCCCO3)CC2)c2ncn(C3CCCCO3)c2n1
title compound
Clc1nc(N[C@H]2CC[C@H](Nc3nc(Cl)nc4c3ncn4C3CCCCO3)CC2)c2ncn(C3CCCCO3)c2n1
Trans-N,N′-bis[2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]-1,4-cyclohexanediamine

Reactants

Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine
Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Adenosine
CCn1nnc([C@@H]2O[C@@H](n3cnc4c(N[C@H]5CC[C@H](Nc6nc(Cl)nc7c6ncn7[C@@H]6O[C@@H](c7nnn(CC)n7)[C@H](CC(=O)[O-])[C@H]6CC(=O)[O-])CC5)nc(Cl)nc43)[C@H](CC(=O)[O-])[C@H]2CC(=O)[O-])n1
Intermediate 1
CCn1nnc([C@@H]2O[C@@H](n3cnc4c(N[C@H]5CC[C@H](Nc6nc(Cl)nc7c6ncn7[C@@H]6O[C@@H](c7nnn(CC)n7)[C@H](CC(=O)[O-])[C@H]6CC(=O)[O-])CC5)nc(Cl)nc43)[C@H](CC(=O)[O-])[C@H]2CC(=O)[O-])n1
Trans-1,4-cyclohexanediylbis[imino(2-chloro-9H-purine-6,9-diyl)(2R,3R,4R,5R)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-2,3,4-triyl]tetraacetate
N[C@H]1CC[C@H](N)CC1
trans-1,4-diaminocyclohexane
CCN(C(C)C)C(C)C
di-iso-propylethylamine

Reagents

None

Solvents

CCCCO
n-butanol

Conditions

Temperature
75°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Temperatureto cool to ambient temperature
  2. 2
    Filtrationfiltered
  3. 3
    Washwashed with n-butanol (2×2.3 L)
  4. 4
    Otherdried in vacuo at 60° C.

Procedure

A stirred suspension of 2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (Intermediate 1 in WO03/080613) (1.14 kg) in n-butanol (1.7 L) was treated with trans-1,4-diaminocyclohexane (239.2 g) and di-iso-propylethylamine (2.5 L), then heated at 75° C. for 17 hours. The suspension was allowed to cool to ambient temperature, filtered, washed with n-butanol (2×2.3 L) and dried in vacuo at 60° C. to give the title compound (0.9 kg).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07737126B2uspto-grants-2010_06