Triethanolamine → (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 923300Notes

Reaction equation

HRID 923300 reaction equation
[NH2:1][C@@H:2]1[CH2:6][C@H:5]([O:7][CH2:8][CH2:9][OH:10])[C@@H:4]([OH:11])[C@H:3]1[OH:12].[Cl:13][C:14]1[C:19]([NH2:20])=[C:18](Cl)[N:17]=[C:16]([S:22][CH2:23][CH2:24][CH3:25])[N:15]=1.[N:26](CCO)(CCO)CCO.N([O-])=O.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[Cl:13][C:14]1[C:19]2[N:20]=[N:26][N:1]([C@@H:2]3[CH2:6][C@H:5]([O:7][CH2:8][CH2:9][OH:10])[C@@H:4]([OH:11])[C@H:3]3[OH:12])[C:18]=2[N:17]=[C:16]([S:22][CH2:23][CH2:24][CH3:25])[N:15]=1

Participants

7

Reactant 4

HCID 7618TriethanolamineHCID 114363364,6-Dichloro-2-(propylthio)pyrimidin-5-amineHCID 23668193Sodium NitriteHCID 71516184Ticagrelor Impurity 27

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 83%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (1S,2S,3R,5S)-3-amino-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLA; 0.89 g, 5 mmol), 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (CLINA; 1.19 g, 5 mmol) and triethanolamine (1.49 g, 10 mmol) was stirred neat for 24 h at 90° C. After cooling to ambient temperature, the viscous reaction mixture was dissolved by the addition of acetic acid (3 mL). While maintaining the reaction temperature at 15-20° C. there was added sodium nitrite (0.38 g, 5.5 mmol) and the reaction mixture left stirring for 12 h. The reaction mixture was diluted with ethyl acetate (35 mL), washed with water (2×25 mL) and evaporated under reduced pressure. The crude product was triturated in hexane (20 mL) and filtered to give CLTOL as an off-white powder (1.61 g, 83% yield): 13C NMR (CDCl3, 125 MHz) δ13.4, 22.0, 33.5, 33.7, 61.75, 61.77, 71.1, 74.9, 75.4, 82.0, 131.8, 150.7, 152.9, 171.8.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. temperatureWhile maintaining the reaction temperature at 15-20° C.
  3. waitthe reaction mixture left
  4. stirringstirring for 12 h
  5. washwashed with water (2×25 mL)
  6. customevaporated under reduced pressure
  7. customThe crude product was triturated in hexane (20 mL)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-d24e98a250b84ad78ba9f57828e1b0c7
Source dataset
uspto-grants-2016_03
Patent number
US09278972B2

Reaction notes

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