Water → HCID 117608693, compound

HRID 1053641Notes

Reaction equation

HRID 1053641 reaction equation
[CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[CH:15]=[O:16])[CH:2]([CH3:4])[CH3:3].[C:17](=O)([O-])[O-].[K+].[K+].CI.O>C(#N)C>[CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH3:17])[N:10]=[C:9]2[CH:15]=[O:16])[CH:2]([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 178450090HCID 178450090, compound

Product 1

HCID 117608693HCID 117608693, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

A mixture of 5-iso-butoxy-1H-indazole-3-carbaldehyde (110 mg, 0.50 mmol, 1.00 equiv), potassium carbonate (209 mg, 1.50 mmol, 2.98 equiv) and methyl iodide (107.5 mg, 0.76 mmol, 1.50 equiv) in acetonitrile (4 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum and the residue was filtered through a silica gel column eluted with 2-5% of ethyl acetate in petroleum ether. The crude product (70 mg) was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005(Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to give 35 mg (30%) of 5-iso-butoxy-1-methyl-1H-indazole-3-carbaldehyde as a white solid. 1H NMR (400 MHz, CDCl3): δ 10.1 (s, 1H), 7.55 (d, J=2.0 Hz, 1H), 7.27 (d, J=8.8 Hz, 1H), 7.07 (dd, J=8.8 Hz, 2.0 Hz, 1H), 4.08 (s, 3H), 3.74 (d, J=6.8 Hz, 2H), 2.09-2.02 (m, 1H), 0.98 (d, J=6.8 Hz, 6H) ppm. LCMS (method D, ESI): RT=2.23 min, m/z=233.1 [M+H]+ and 15 mg (13%) of 5-iso-butoxy-2-methyl-2H-indazole-3-carbaldehyde as a white solid. 1H NMR (400 MHz, CDCl3): 10.12 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.17 (d, J=2.4 Hz, 1H), 7.07 (dd, J=9.2 Hz, 2.4 Hz, 1H), 4.38 (s, 3H), 3.73 (d, J=6.4 Hz, 2H), 2.10-2.05 (m, 1H), 0.99 (d, J=6.8 Hz, 6H) ppm. LCMS (method D, ESI): RT=2.24 min, m/z=233.1 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. filtrationthe residue was filtered through a silica gel column
  3. washeluted with 2-5% of ethyl acetate in petroleum ether
  4. customThe crude product (70 mg) was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005(Waters))
  5. waitup to 95% in 1 min
  6. waitdown to 18% in 2 min)

Sources & evidence

ORD record
ord-31b7272febed45219ca4389cb9ce1cf6
Source dataset
uspto-grants-2016_07
Patent number
US09394258B2

Reaction notes

Loading…