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

HRID 69311Notes

Reaction equation

HRID 69311 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.[Cl:19][C:20]1[C:25]2[CH:26]=[N:27][NH:28][C:24]=2[CH:23]=[CH:22][N:21]=1>ClCCl>[Cl:19][C:20]1[C:25]2[CH:26]=[N:27][N:28]([CH:18]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:24]=2[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 468356374-chloro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 867178134-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

p-Toluenesulfonic acid monohydrate (2.4 g, 13 mmol) and 3,4-dihydro-2H-pyran (99%, 45 mL, 520 mmol) were sequentially added to a suspension of 4-chloro-1H-pyrazolo[4,3-c]pyridine (20.0 g, 130 mmol) in dichloromethane (400 mL). The reaction mixture was allowed to stir at room temperature for 24 hours, at which time it was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluents: 10%, then 30%, then 50% ethyl acetate in heptane) afforded the product as a white solid. Yield: 27.51 g, 115.7 mmol, 89%. LCMS m/z 238.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J=6.0 Hz, 1H), 8.16 (d, J=0.9 Hz, 1H), 7.47 (dd, J=6.0, 0.9 Hz, 1H), 5.73 (br dd, J=9.0, 2.7 Hz, 1H), 3.97-4.04 (m, 1H), 3.72-3.80 (m, 1H), 2.43-2.53 (m, 1H), 2.07-2.20 (m, 2H), 1.65-1.85 (m, 3H).

Workup

  1. washwas washed with saturated aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification via silica gel chromatography (Eluents

Sources & evidence

ORD record
ord-eb6d71f75c5b4a9ba21b71a5ac3fb4bc
Source dataset
uspto-grants-2014_09
Patent number
US08822494B2

Reaction notes

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