Hydrochloric Acid → (R)-1-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol

HRID 534122Notes

Reaction equation

HRID 534122 reaction equation
CC1(C)[O:6][C@H:5]([C:7]2[N:11]=[C:10]([NH:12][C:13]3[C:18]([O:19][C:20]4[C:21]([CH3:26])=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:17][C:16]([S:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[CH:15][N:14]=3)[S:9][N:8]=2)[CH2:4][O:3]1.Cl>C(O)C>[CH3:26][C:21]1[C:20]([O:19][C:18]2[C:13]([NH:12][C:10]3[S:9][N:8]=[C:7]([C@@H:5]([OH:6])[CH2:4][OH:3])[N:11]=3)=[N:14][CH:15]=[C:16]([S:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[CH:17]=2)=[CH:25][CH:24]=[CH:23][N:22]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68477969(R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 25235319(R)-1-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diolYield 82.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A flask was charged with (R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-1,2,4-thiadiazol-5-amine (3.8 g, 7.683 mmol) and added ethanol (40 mL). 3M HCl (5.122 ml, 15.37 mmol) was added, and the reaction was heated to 70° C. for 1 hour, then cooled to ambient temperature. The ethanol removed in vacuo and saturated sodium bicarbonate solution was added. The aqueous layer was extracted with ethyl acetate. The majority of product crashed out of the aqueous layer and collected by filtration. The solids and residue from organic layer were purified over silica get (10-15% methanol in ethyl acetate) to afford (R)-1-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol (2.877 g, 6.330 mmol, 82.38% yield) as yellow solid. Mass Spectrum (apci) m/z=455.1 (M+H).

Workup

  1. temperaturecooled to ambient temperature
  2. customThe ethanol removed in vacuo and saturated sodium bicarbonate solution
  3. additionwas added
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. filtrationcollected by filtration
  6. customThe solids and residue from organic layer were purified over silica
  7. customget (10-15% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-54aba4eb84564f11bdecce07ddd8a9a2
Source dataset
uspto-grants-2014_10
Patent number
US08853409B2

Reaction notes

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