Ammonia → HCID 86686988, compound

HRID 2284958Notes

Reaction equation

HRID 2284958 reaction equation
Cl[C:2]1[N:6]2[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.[OH:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.N>CC(N(C)C)=O.CO.C(Cl)Cl>[F:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([N:16]3[CH2:17][CH2:18][CH:13]([OH:12])[CH2:14][CH2:15]3)=[N:3][N:4]=2)[CH:7]=1

Participants

7

Reactant 3

HCID 222AmmoniaHCID 79341Piperidin-4-olHCID 552675403-Chloro-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 86686988HCID 86686988, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A brown solution of Intermediate 24b (855 mg, 4.98 mmol) and 4-hydroxypiperidine (2.02 g, 19.9 mmol) in DMA (15 mL) was irradiated to 175° C. in the microwave for 3 h. The cooled solution was concentrated in vacuo, then the residue diluted with water (20 mL) and brine (20 mL). The mixture was washed with diethyl ether (2×50 mL), then extracted with EtOAc (2×50 mL). The combined EtOAc layers were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave a yellow oil. The aqueous was further extracted with DCM (3×50 mL). The combined DCM layers were passed through a hydrophobic frit and concentrated in vacuo to leave a brown oil. The two oils were combined. FCC, using 4-5% [2M NH3 in MeOH] in DCM, gave the title compound as a yellow crystalline solid (514 mg, 44%). LCMS (Method 3): Rt 1.96 min, m/z 237 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. additionthe residue diluted with water (20 mL) and brine (20 mL)
  3. washThe mixture was washed with diethyl ether (2×50 mL)
  4. extractionextracted with EtOAc (2×50 mL)
  5. washThe combined EtOAc layers were washed with brine (50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto leave a yellow oil
  10. extractionThe aqueous was further extracted with DCM (3×50 mL)
  11. concentrationconcentrated in vacuo
  12. customto leave a brown oil

Sources & evidence

ORD record
ord-717f0a2dc52f45a79f4e08199017c347
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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