Ethylene Glycol → HCID 66584734, compound

HRID 2369012Notes

Reaction equation

HRID 2369012 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]1[CH:13]=[N:14][N:15]3[C:20]([N:21](COCC[Si](C)(C)C)COCC[Si](C)(C)C)=[CH:19][C:18]([CH:38]([NH:40][CH:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH3:39])=[N:17][C:16]=13)=[CH:5]2.Cl.C(O)CO.C([O-])(O)=O.[Na+]>O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]1[CH:13]=[N:14][N:15]3[C:20]([NH2:21])=[CH:19][C:18]([CH:38]([NH:40][CH:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[CH3:39])=[N:17][C:16]=13)=[CH:5]2

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 66584551HCID 66584551, compound

Product 1

HCID 66584734HCID 66584734, compoundYield 94.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A stirred solution of 3-(6-fluoroquinolin-3-yl)-5-[1-(tetrahydro-2H-pyran-4-ylamino)ethyl]-N,N-bis{[2-(trimethylsilyl)ethoxy]methyl}pyrazolo[1,5-a]pyrimidin-7-amine (890 mg, 1.33 mmol) in dioxane (4 mL) was treated with 4 M HCl in dioxane (4 mL) followed by 1,2-ethanediol (4 mL), and the resulting amber mixture was stirred at room temperature for 15 min and then at 50° C. for 5 h at which point the reaction was near completion. The mixture was cooled to room temperature, added carefully in portions to saturated aqueous NaHCO3 (200 mL) with stirring, and extracted with DCM (3×100 mL). The combined organic phase was washed with water (100 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The solid residue was taken up in 10% MeOH/DCM (˜7-8 mL), diluted with diethyl ether (˜40 mL) and the small amount of precipitate that formed was removed by filtration through a fine frit. The filtrate was concentrated under reduced pressure to give 3-(6-fluoroquinolin-3-yl)-5-(1-(tetrahydro-2H-pyran-4-ylamino)ethyl)pyrazolo[1,5-a]pyrimidin-7-amine (510 mg, 80% yield @ 85% purity) as a tan amorphous solid. MS (ESI+) for C22H23FN6O m/z 407 (MAI); HPLC, 2.43 min (Method B).

Workup

  1. waitat 50° C. for 5 h at which point
  2. temperatureThe mixture was cooled to room temperature
  3. stirringwith stirring
  4. extractionextracted with DCM (3×100 mL)
  5. washThe combined organic phase was washed with water (100 mL) and brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. additiondiluted with diethyl ether (˜40 mL)
  9. customthe small amount of precipitate that formed
  10. customwas removed by filtration through a fine frit
  11. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ff01c6143e7b404e929dbffde97622d8
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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