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

HRID 69313Notes

Reaction equation

HRID 69313 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]=[C:22]([CH3:29])[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]=[C:22]([CH3:29])[N:21]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 730127754-Chloro-6-methyl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 867178144-Chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

p-Toluenesulfonic acid monohydrate (29 mg, 0.15 mmol) and 3,4-dihydro-2H-pyran (99%, 205 μL, 2.39 mmol) were sequentially added to a suspension of C1 (250 mg, 1.49 mmol) and 4 Å molecular sieves in dichloromethane (10 mL). The reaction mixture was allowed to stir at room temperature for 4 hours, at which time it was filtered, concentrated in vacuo, and washed three times with heptane. Purification via silica gel chromatography (Gradient: 20% to 50% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 65 mg, 0.26 mmol, 17%. LCMS m/z 252.1 [M+H+]. 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 8.08 (d, J=0.9 Hz, 1H), 7.26-7.27 (m, 1H), 5.67 (dd, J=9.1, 2.8 Hz, 1H), 3.99-4.05 (m, 1H), 3.71-3.79 (m, 1H), 2.65 (d, J=0.8 Hz, 3H), 2.06-2.2 (m, 2H).

Workup

  1. filtrationwas filtered
  2. concentrationconcentrated in vacuo
  3. washwashed three times with heptane
  4. customPurification via silica gel chromatography (Gradient: 20% to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-099668b262344b5fafc735f46bb6ba04
Source dataset
uspto-grants-2014_09
Patent number
US08822494B2

Reaction notes

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