Sodium Bicarbonate → 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 589819Notes

Reaction equation

HRID 589819 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.C(=O)(O)[O-].[Na+]>CCCCCC.O.C(OCC)(=O)C>[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 3

HCID 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 95%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (25 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 (42.5 g), water (75 mL) and sodium bicarbonate (53 g). The mixture was heated to about 100° C. and maintained at the same temperature for about 14 hours and completion of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to 60° C. followed by addition of ethyl acetate (25 mL), water (175 mL) and n-hexane (375 mL). The mixture was stirred for about 7 hours. The solid obtained was isolated by filtration and washed with water (50 mL). The wet compound and water (500 mL) were charged into round bottom flask and stirred for overnight. The solid was isolated by filtration and washed with water (50 mL) and was subjected to drying under vacuum at 60° C. for 9 hours to afford the title compound in about 95% yield having HPLC purity of about 98.5%.

Workup

  1. temperaturemaintained at the same temperature for about 14 hours
  2. customAfter completion of reaction
  3. temperaturethe mixture was cooled to 60° C.
  4. customThe solid obtained
  5. customwas isolated by filtration
  6. washwashed with water (50 mL)
  7. additionThe wet compound and water (500 mL) were charged into round bottom flask
  8. stirringstirred for overnight
  9. customThe solid was isolated by filtration
  10. washwashed with water (50 mL)
  11. customto drying under vacuum at 60° C. for 9 hours

Sources & evidence

ORD record
ord-47feab08eaf946ebbff18ee6213f3e80
Source dataset
uspto-grants-2016_01
Patent number
US09233966B2

Reaction notes

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