Sodium Nitrite → (1S,2S,3R,5S)-3-(7-Chloro-5-(Propylthio)-3H-[1,2,3]Triazolo[4,5-d]Pyrimidin-3-Yl)-5-(2-Hydroxyethoxy)Cyclopentane-1,2-Diol

HRID 923302Notes

Reaction equation

HRID 923302 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([S:8][CH2:9][CH2:10][CH3:11])[N:5]=[C:4]([NH:12][C@@H:13]2[CH2:17][C@H:16]([O:18][CH2:19][CH2:20][OH:21])[C@@H:15]([OH:22])[C@H:14]2[OH:23])[C:3]=1[N+:24]([O-])=O.[H][H].[N:29]([O-])=O.[Na+]>C(O)(=O)C.[Pt].C(OCC)(=O)C>[Cl:1][C:2]1[C:3]2[N:24]=[N:29][N:12]([C@@H:13]3[CH2:17][C@H:16]([O:18][CH2:19][CH2:20][OH:21])[C@@H:15]([OH:22])[C@H:14]3[OH:23])[C:4]=2[N:5]=[C:6]([S:8][CH2:9][CH2:10][CH3:11])[N:7]=1

Participants

7

Reactant 3

HCID 23668193Sodium NitriteHCID 71609808(1S,2S,3R,5S)-3-((6-chloro-5-nitro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diolHCID 178418361HCID 178418361, compound

Product 1

HCID 71609809(1S,2S,3R,5S)-3-(7-Chloro-5-(Propylthio)-3H-[1,2,3]Triazolo[4,5-d]Pyrimidin-3-Yl)-5-(2-Hydroxyethoxy)Cyclopentane-1,2-DiolYield 71.3%

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

The solution of (1S,2S,3R,5S)-3-((6-chloro-5-nitro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLACIN; 0.74 g, 1.8 mmol) in acetic acid (15 mL) was hydrogenated for 5 h in the presence of platinum on carbon (5%; 0.11 g, 1.5 mol %) at 10 bar hydrogen pressure. The catalyst was filtered trough celite and washed with ethyl acetate (5 mL). The analysis of the filtrate confirmed complete conversion of the starting material and 95 area % HPLC purity of the intermediate (1S,2S,3R,5S)-3-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLACINA). To the filtrate was then added sodium nitrite (0.14 g, 2 mmol) while stirring in a bath at 15-20° C. After 1 h, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (2×50 mL) and evaporated under reduced pressure. The solid residue was triturated in n-hexane (10 mL) and filtered to give CLTOL as a grey powder (0.50 g, 71% yield): 96 area % by HPLC; mp 91-95° C.

Workup

  1. filtrationThe catalyst was filtered trough celite
  2. washwashed with ethyl acetate (5 mL)
  3. washwashed with water (2×50 mL)
  4. customevaporated under reduced pressure
  5. customThe solid residue was triturated in n-hexane (10 mL)
  6. filtrationfiltered

Sources & evidence

ORD record
ord-3f335dc41d6349639edbd4a36b765019
Source dataset
uspto-grants-2016_03
Patent number
US09278972B2

Reaction notes

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