p-Toluenesulfonic acid → methyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

HRID 1529441Notes

Reaction equation

HRID 1529441 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[I:14])=[O:4].[O:15]1[CH:20]=[CH:19][CH2:18][CH2:17][CH2:16]1.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][O:15]1)[N:9]=[C:8]2[I:14])=[O:4]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 178497396HCID 178497396, compound

Product 1

HCID 67959982methyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylateYield 58.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In 50 mL R. B. flask, to a solution of 3-iodo-1H-indazole-5-carboxylic acid methyl ester (0.2 g, 0.66 mmol) in DCM (10 mL) was added 3,4-dihydropyran (0.117 g, 1.32 mmol) at 5° C. followed by the addition of PTSA (0.038 g, 0.264 mmol). The reaction was stirred for 2 h at RT, quenched with water (25 mL) and extracted with DCM (50 mL). The organic layer was separated and washed with water (2×25 mL) and dried over anhydrous Na2SO4, filtered and concentrated. The residue was triturated with n-pentane to give 3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole-5-carboxylic acid methyl ester (0.15 g, 58%) as off white solid. MS (ESI, pos. ion) m/z: 302.7 (M-THP+1); 1H-NMR (300 MHz DMSO-d6): δ ppm 8.24 (t, 1 H, J=9 Hz), 8.13 (dd, 1 H, J=8.7, 1.5 Hz), 7.60 (d, 1 H, J=9 Hz), 5.73 (dd, 1 H, J=9.6, 2.7 Hz), 4.95 (m, 1H), 3.96-4.04 (m, 4H), 3.75-3.78 (m, 1H), 3.52-3.53 (m, 1H), 2.52-2.56 (m, 1H), 2.05-2.17 (m, 2H), 1.58-1.84 (m, 4H).

Workup

  1. customquenched with water (25 mL)
  2. extractionextracted with DCM (50 mL)
  3. customThe organic layer was separated
  4. washwashed with water (2×25 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was triturated with n-pentane

Sources & evidence

ORD record
ord-b9e8320c94ac4fd48266faf252e71c1d
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

Loading…