3,4-dihydro-2H-pyran → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-3-(trifluoromethyl)-1H-indazole

HRID 77453Notes

Reaction equation

HRID 77453 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([F:14])([F:13])[F:12].[O:15]1[CH:20]=[CH:19][CH2:18][CH2:17][CH2:16]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][O:15]1)[N:6]=[C:5]2[C:11]([F:14])([F:13])[F:12]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178506287HCID 178506287, compound

Product 1

HCID 866797385-bromo-1-(tetrahydro-2H-pyran-2-yl)-3-(trifluoromethyl)-1H-indazoleYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-bromo-3-(trifluoromethyl)-1H-indazole (500 mg, 1.887 mmol) in DCM (10 mL) was added 3,4-dihydro-2h-pyran (0.517 mL, 5.66 mmol) and p-toluenesulfonic acid monohydrate (35.9 mg, 0.189 mmol). The solution was stirred for 1 h. The solution was diluted with DCM, washed with saturated NaHCO3 and concentrated. The residue was purified by flash chromatography on silica gel with eluting with 10% EtOAc/Hexane to give 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-3-(trifluoromethyl)-1H-indazole as a colorless oil (610 mg, 93%). 1NMR: 400 MHz, CDCl3: δ ppm 1.69-1.75 (m, 7H), 2.12-2.17 (m, 2H), 2.48-2.51 (m, 1H), 3.61 (d, J=85.20 Hz, 3H), 3.72-3.78 (m, 2H), 3.87-3.99 (m, 3H), 4.56 (s, 1H), 5.77 (dd, J=4.00, 8.00 Hz, 1H), 7.52-7.60 (m, 2H), 7.96 (t, J=24.40 Hz, 1H).

Workup

  1. washwashed with saturated NaHCO3
  2. concentrationconcentrated
  3. customThe residue was purified by flash chromatography on silica gel
  4. washwith eluting with 10% EtOAc/Hexane

Sources & evidence

ORD record
ord-be038ba96f3341c890ff2bc098247c8b
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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