Triethylamine → (1S,2S,3R,5S)-3-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

HRID 923297Notes

Reaction equation

HRID 923297 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.C(N(CC)CC)C>C(OCC)(=O)C.CCCCCC>[NH2:20][C:19]1[C:18]([NH:1][C@@H:2]2[CH2:6][C@H:5]([O:7][CH2:8][CH2:9][OH:10])[C@@H:4]([OH:11])[C@H:3]2[OH:12])=[N:17][C:16]([S:22][CH2:23][CH2:24][CH3:25])=[N:15][C:14]=1[Cl:13]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 114363364,6-Dichloro-2-(propylthio)pyrimidin-5-amineHCID 71516184Ticagrelor Impurity 27

Product 1

HCID 71609773(1S,2S,3R,5S)-3-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diolYield 88%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (1S,2S,3R,5S)-3-amino-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLA; 1.06 g, 6 mmol), 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (CLINA; 1.43 g, 6 mmol), triethylamine (1.09 g, 7.8 mmol) and polyethyleneglycol PEG400 (2 mL) was stirred for 48 h at 75° C. The reaction mixture was diluted with ethyl acetate (50 mL), washed with water (25 mL) and evaporated under reduced pressure to give a resinous material which solidified upon trituration in n-hexane (25 mL). After filtration there was obtained OLACINA as a grey powder (2.0 g, 88% yield): 13C NMR (DMSO-d6, 125 MHz) δ13.3, 22.8, 32.2, 34.7, 54.8, 60.4, 69.8, 72.4, 75.2, 82.4, 119.9, 137.5, 152.5, 155.1.

Workup

  1. washwashed with water (25 mL)
  2. customevaporated under reduced pressure
  3. customto give a resinous material which
  4. filtrationAfter filtration

Sources & evidence

ORD record
ord-518cd1e9e65644dcb14a2d2775e41492
Source dataset
uspto-grants-2016_03
Patent number
US09278972B2

Reaction notes

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