Methanesulfonic Acid → 6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine

HRID 1778683Notes

Reaction equation

HRID 1778683 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][NH:10][C:4]=2[CH:3]=1.C1COCC1.CS(O)(=O)=O.[O:21]1[CH:26]=[CH:25][CH2:24][CH2:23][CH2:22]1>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26][O:21]3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 569321096-Chloro-1H-pyrazolo(4,3-c)pyridine

Product 1

HCID 714636356-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridineYield 112.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At r.t. to a suspension of 6-chloro-1H-pyrazolo[4,3-c]pyridine (0.5 g, 3 mmol) (Frontier Cat. No. Z13659) in methylene chloride (3 mL) and THF (1 mL) was added methanesulfonic acid (42 μL, 0.65 mmol), followed by dihydropyran (0.89 mL, 9.8 mmol). The mixture was stirred at r.t. for 2 h., and then at 50° C. overnight. After cooling the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (0.8 g). LCMS (M+H)+=238.0; LCMS (M-84+H)+=154.0/156.0.

Workup

  1. customat 50° C.
  2. customovernight
  3. temperatureAfter cooling the mixture
  4. concentrationwas concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%)

Sources & evidence

ORD record
ord-7c47d81698804d49ab4c52564c4bff90
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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