Anisole → HCID 178527276, compound

HRID 1711397Notes

Reaction equation

HRID 1711397 reaction equation
OS(C(F)(F)F)(=O)=O.C(OC([N:19]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[C:28]3[S:34]([C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH:40]=[CH:39][CH:38]=2)(=[O:36])=[O:35])[CH2:20]1)=O)C1C=CC=CC=1.C1(OC)C=CC=CC=1.[OH-].[Na+]>C(Cl)Cl>[C:37]1([S:34]([C:28]2[C:27]3[C:31](=[CH:32][CH:33]=[C:25]([O:24][CH:21]4[CH2:22][CH2:23][NH:19][CH2:20]4)[CH:26]=3)[NH:30][N:29]=2)(=[O:35])=[O:36])[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 7519AnisoleHCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 178525143HCID 178525143, compound

Product 1

HCID 178527276HCID 178527276, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triflic acid (1.6 mL, 18 mmol) was added to a solution of 3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-pyrrolidine-1-carboxylic acid benzyl ester (1.35 g, 2.56 mmol) and anisole (0.83 mL, 7.7 mmol) in methylene chloride at 0° C. The reaction mixture was stirred at 0° C., under nitrogen, for 3.5 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 0.5-1.0% ammonium hydroxide/5.0-10% methanol in chloroform to give 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole as a beige solid, 0.684 g (67.7% yield), mp 168-170° C. dec. A portion of the solid (110 mg) was treated with methanol and ethereal HCl; chloroform and more methanol were then added for better solubility. The resultant mixture was concentrated to dryness in vacuo at 82° C. for 12 hours to yield the title product as a cream-colored foam (0.108 g); Mass spectrum (+EI, [M+H]+) m/z 394. 1HNMR (500 MHz, DMSO-d6): δ14.15-14.28 (br, 1H), 9.21-9.45 (br, 2H), 8.74-8.76 (m, 1H), 8.56 (dd, 1H, J=7.32 Hz and 1.22 Hz), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.04 (m, 1H), 7.71-7.75 (m, 1H), 7.55-7.64 (m, 3H), 7.29 (d, 1H, J=2.20 Hz), 7.11 (dd, 1H, J=9.15 Hz and 2.31 Hz), 5.19-5.21 (m, 1H), 3.43-3.47 (m, 1H), 3.28-3.34 (m, 2H), 2.16-2.25 (m, 1H), 2.04-2.10 ppm (m, 1H).

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 0.5-1.0% ammonium hydroxide/5.0-10% methanol in chloroform

Sources & evidence

ORD record
ord-b4b4ae8e4bed4b4e82af2b794ce2f594
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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