Dimethyl Sulfoxide → 2-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol

HRID 589815Notes

Reaction equation

HRID 589815 reaction equation
Cl[C:2]1[C:7]([NH2:8])=[C:6]([Cl:9])[N:5]=[C:4]([S:10][CH2:11][CH2:12][CH3:13])[N:3]=1.C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.[NH2:24][C@H:25]1[C@@H:29]2[O:30][C:31]([CH3:34])([CH3:33])[O:32][C@@H:28]2[C@@H:27]([O:35][CH2:36][CH2:37][OH:38])[CH2:26]1.CS(C)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.O>[NH2:8][C:7]1[C:2]([NH:24][C@H:25]2[C@@H:29]3[O:30][C:31]([CH3:33])([CH3:34])[O:32][C@@H:28]3[C@@H:27]([O:35][CH2:36][CH2:37][OH:38])[CH2:26]2)=[N:3][C:4]([S:10][CH2:11][CH2:12][CH3:13])=[N:5][C:6]=1[Cl:9]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 516892Sodium BicarbonateHCID 114363364,6-Dichloro-2-(propylthio)pyrimidin-5-amineHCID 722066542-{[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy}ethanol (2R,3R)-2,3-dihydroxysuccinate

Product 1

HCID 102021862-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanolYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
62.5 °C

Procedure

A flask was charged with 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (3 g), 2-(((3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol L-tartaric acid salt (5.1 g), dimethyl sulfoxide (30 mL) and sodium bicarbonate (6.3 g). The mixture was heated to about 60-65° C. and maintained at the same temperature for about 10 hours and completion of the reaction was monitored by TLC. After completion of reaction the mixture was cooled to 25-30° C. followed by addition of water (30 mL) and toluene (30 mL). The mixture was stirred for about 10 minutes and layers were separated. The organic layer was with water (30 mL). The organic layer was separated and subjected to complete distillation under vacuum at 55-60° C. followed by cooling to room temperature and subsequent addition of n-hexane (45 mL). The mixture was stirred for about 3 hours at room temperature followed by isolation of solid by filtration and washing with n-hexane (15 mL). The solid isolated was subjected to drying under vacuum at 55-60° C. for about 4 hours to afford the title compound in about 78% yield having HPLC purity of about 98%.

Workup

  1. temperaturemaintained at the same temperature for about 10 hours
  2. customAfter completion of reaction the mixture
  3. temperaturewas cooled to 25-30° C.
  4. customlayers were separated
  5. customThe organic layer was separated
  6. distillationsubjected to complete distillation under vacuum at 55-60° C.
  7. temperatureby cooling to room temperature
  8. additionsubsequent addition of n-hexane (45 mL)
  9. stirringThe mixture was stirred for about 3 hours at room temperature
  10. filtrationfollowed by isolation of solid by filtration
  11. washwashing with n-hexane (15 mL)
  12. customThe solid isolated
  13. customto drying under vacuum at 55-60° C. for about 4 hours

Sources & evidence

ORD record
ord-cc778608d27a4294ae978781a7533f17
Source dataset
uspto-grants-2016_01
Patent number
US09233966B2

Reaction notes

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