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

HRID 923301Notes

Reaction equation

HRID 923301 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([Cl:11])[N:5]=[C:4]([S:12][CH2:13][CH2:14][CH3:15])[N:3]=1.[NH2:16][C@@H:17]1[CH2:21][C@H:20]([O:22][CH2:23][CH2:24][OH:25])[C@@H:19]([OH:26])[C@H:18]1[OH:27].C(N(CC)CC)C>O1CCCC1.CN1CCCC1=O.C(OCC)(=O)C>[Cl:11][C:6]1[N:5]=[C:4]([S:12][CH2:13][CH2:14][CH3:15])[N:3]=[C:2]([NH:16][C@@H:17]2[CH2:21][C@H:20]([O:22][CH2:23][CH2:24][OH:25])[C@@H:19]([OH:26])[C@H:18]2[OH:27])[C:7]=1[N+:8]([O-:10])=[O:9]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 222689244,6-Dichloro-5-nitro-2-(propylthio)pyrimidineHCID 71516184Ticagrelor Impurity 27

Product 1

HCID 71609808(1S,2S,3R,5S)-3-((6-chloro-5-nitro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diolYield 70.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (CLIN; 0.80 g, 3 mmol) in tetrahydrofuran (30 mL) at 0° C. was slowly added a solution of (1S,2S,3R,5S)-3-amino-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLA; 0.53 g, 3 mmol) in N-methylpyrrolidin-2-one (5 mL). After 10 min there was added triethylamine (0.42 mL, 3 mmol) and the mixture left stirring for 3 h at 0° C. and then 16 h at 20° C. The reaction mixture was diluted with ethyl acetate (60 mL), washed with water (2×60 mL) and evaporated under reduced pressure. The obtained crude product was triturated under diisopropyl ether (10 mL) and filtered to give OLACIN as a yellow powder (0.86 g, 70% yield): 98 area % by HPLC; mp 94-98° C.; 13C NMR (CDCl3, 125 MHz) δ13.2, 22.3, 32.7, 33.6, 55.7, 60.3, 70.7, 74.0, 74.6, 82.5, 124.5, 151.6, 153.9, 171.9.

Workup

  1. waitthe mixture left
  2. custom16 h
  3. customat 20° C
  4. washwashed with water (2×60 mL)
  5. customevaporated under reduced pressure
  6. customThe obtained crude product
  7. customwas triturated under diisopropyl ether (10 mL)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-8c49bf8da722486bb9359792835d6026
Source dataset
uspto-grants-2016_03
Patent number
US09278972B2

Reaction notes

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