Anisole → HCID 178527277, compound

HRID 1711407Notes

Reaction equation

HRID 1711407 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][N:22]=[C:21]3[S:27]([C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:33]=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.C1(OC)C=CC=CC=1.OS(C(F)(F)F)(=O)=O.[OH-].[Na+]>C(Cl)Cl>[C:30]1([S:27]([C:21]2[C:20]3[C:24](=[CH:25][CH:26]=[C:18]([O:17][CH:14]4[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]4)[CH:19]=3)[NH:23][N:22]=2)(=[O:28])=[O:29])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 7519AnisoleHCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 178525144HCID 178525144, compound

Product 1

HCID 178527277HCID 178527277, compoundYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-[3-(1-naphthylsulfonyl)-1H-indazol-5-yloxy]piperidin-1-ylcarboxylic acid benzyl ester (1.78 g, 3.29 mmol) and anisole (1.1 mL, 9.9 mmol) in methylene chloride at 0° C. was treated with triflic acid (2.05 mL, 23.2 mmol), stirred at 0° C. under nitrogen for 1.5 hours, treated with 2.5 N sodium hydroxide and extracted with warm ethyl acetate. The extracts were combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography with 0.5-0.75% ammonium hydroxide/5.0-7.5% methanol in chloroform to give 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole as a dark orange semi-solid, 0.860 g, (64.2% yield). A portion of the semi-solid (160 mg) was dispersed in methanol and chloroform, treated with ethereal HCl and concentrated in vacuo for 12 hours at 82° C. to yield the title product as a light orange solid, 0.151 g, mp 174-6° C. (dec), Mass spectrum (+EI, [M+H]+) m/z 408. 1HNMR (500 MHz, DMSO-d6): δ14.11-14.19 (br, 1H), 8.66-8.80 (br, m, 3H), 8.55-8.57 (m, 1H), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.04 (m, 1H), 7.70-7.73 (m, 1H), 7.54-7.63 (m, 3H), 7.31 (d, 1H, J=2.07 Hz), 7.12-7.15 (m, 1H), 4.69-4.73 (m, 1H), 3.19-3.29 (m, 2H), 3.06-3.13 (m, 2H), 2.02-2.07 (m, 2H), 1.75-1.83 ppm (m, 2H).

Workup

  1. extractionextracted with warm ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography with 0.5-0.75% ammonium hydroxide/5.0-7.5% methanol in chloroform

Sources & evidence

ORD record
ord-8ce8d8891f6d413e9f3ac2276c3638fe
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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