Anisole → HCID 71557176, compound

HRID 2203426Notes

Reaction equation

HRID 2203426 reaction equation
[Cl:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[C:12]([F:13])=[CH:11][C:10]([S:14]([N:17](CC3C=CC(OC)=CC=3OC)[C:18]3[S:22][N:21]=[CH:20][N:19]=3)(=[O:16])=[O:15])=[C:9]([F:34])[CH:8]=2)=[C:4]([C:37]2[N:42]3[CH:43]=[N:44][CH:45]=[C:41]3[C:40](=[O:46])[N:39](CC3C=CC(OC)=CC=3)[CH:38]=2)[CH:3]=1.C1(OC)C=CC=CC=1.FC(F)(F)S(O)(=O)=O>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[C:12]([F:13])=[CH:11][C:10]([S:14]([NH:17][C:18]3[S:22][N:21]=[CH:20][N:19]=3)(=[O:15])=[O:16])=[C:9]([F:34])[CH:8]=2)=[C:4]([C:37]2[N:42]3[CH:43]=[N:44][CH:45]=[C:41]3[C:40](=[O:46])[NH:39][CH:38]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 7519AnisoleHCID 62406Trifluoromethanesulfonic acidHCID 90389190HCID 90389190, compound

Product 1

HCID 71557176HCID 71557176, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 4-(4-chloro-2-(7-(4-methoxybenzyl)-8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.20 g, 0.25 mmol) and anisole (0.54 mL, 5.0 mmol) in trifluoroacetic acid (2 mL) at 0° C. was added trifluoromethanesulfonic acid (0.22 mL, 2.5 mmol). The reaction mixture was allowed to warm to ambient temperature, stirred for 16 h and concentrated in vacuo. The residue was partitioned between dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL). The aqueous phase was washed with dichloromethane (2×30 mL), acidified to pH 3-4 with 1 M hydrochloric acid and extracted with ethyl acetate (5×40 mL). The combined ethyl acetate extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was triturated in ethyl acetate/diethyl ether (5/95 v/v) to afford 4-(4-chloro-2-(8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as an off-white solid in 77% yield (0.104 g): 1H NMR (300 MHz, DMSO-d6) δ11.22 (d, J=4.8 Hz, 1H), 8.55 (s, 1H), 8.49 (br s, 1H), 8.11 (br s, 1H), 7.80 (s, 1H), 7.76-7.63 (m, 2H), 7.41-7.29 (m, 2H), 6.95 (d, J=5.3 Hz, 1H); MS (ES+) m/z 536.7 (M+1), 538.7 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between dichloromethane (30 mL) and saturated aqueous sodium bicarbonate (30 mL)
  3. washThe aqueous phase was washed with dichloromethane (2×30 mL)
  4. extractionextracted with ethyl acetate (5×40 mL)
  5. dry with materialThe combined ethyl acetate extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated in ethyl acetate/diethyl ether (5/95 v/v)

Sources & evidence

ORD record
ord-f53029a4c7594cbb83ca6c0436cd7457
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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