Reaction #742302

ord-ce25e97303a7476c9d5549dbc70ce080

Reaction equation

Cl
HCl
CCc1cc([C@H]2O[C@@H](n3cnc4c(Cl)nc(Cl)nc43)[C@H](OC(C)=O)[C@@H]2OC(C)=O)on1
acetic acid (2R,3R,4R,5S)-4-acetoxy-2-(2,6-dichloro-purin-9-yl)-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3-yl ester
N[C@H](CO)Cc1ccccc1
(S)-2-amino-3-phenyl-propan-1-ol
CCN(C(C)C)C(C)C
DIPEA
→
CCc1cc([C@H]2O[C@@H](n3cnc4c(N[C@H](CO)Cc5ccccc5)nc(Cl)nc43)[C@H](OC(C)=O)[C@@H]2OC(C)=O)on1.Cl
title compound
CCc1cc([C@H]2O[C@@H](n3cnc4c(N[C@H](CO)Cc5ccccc5)nc(Cl)nc43)[C@H](OC(C)=O)[C@@H]2OC(C)=O)on1.Cl
Acetic acid (2R,3R,4R,5S)-4-acetoxy-2-[6-((S)-1-benzyl-2-hydroxy-ethylamino)-2-chloro-purin-9-yl]-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3-yl ester hydrochloride

Reactants

Cl
HCl
CCc1cc([C@H]2O[C@@H](n3cnc4c(Cl)nc(Cl)nc43)[C@H](OC(C)=O)[C@@H]2OC(C)=O)on1
acetic acid (2R,3R,4R,5S)-4-acetoxy-2-(2,6-dichloro-purin-9-yl)-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3-yl ester
N[C@H](CO)Cc1ccccc1
(S)-2-amino-3-phenyl-propan-1-ol
CCN(C(C)C)C(C)C
DIPEA

Reagents

None

Solvents

ClCCCl
DCE

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.ADDITIONis added
  2. 2
    Otherthe organic portion is separated
  3. 3
    Concentrationconcentrated in vacuo

Procedure

A mixture comprising acetic acid (2R,3R,4R,5S)-4-acetoxy-2-(2,6-dichloro-purin-9-yl)-5-(3-ethyl-isoxazol-5-yl)-tetrahydro-furan-3-yl ester (WO 99/38877) (1 g, 2.13 mmol), (S)-2-amino-3-phenyl-propan-1-ol (0.321 g, 2.13 mmol) and DIPEA (0.275 g, 2.13 mmol) in DCE (5 mL) is stirred under an inert atmosphere of argon overnight. After cooling to room temperature (RT), 1 M HCl is added, the organic portion is separated and concentrated in vacuo to afford the title compound which is used in the next step without further purification. (MH+585.1)

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08071565B2uspto-grants-2011_12