Sodium Hydroxide → HCID 10160063, compound

HRID 1766271Notes

Reaction equation

HRID 1766271 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:12])=[CH:8][C:9]=2[CH3:11])[C:4]([CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:3]1.[H-].[Na+].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[S:30](Cl)(=[O:32])=[O:31].[OH-].[Na+]>C1COCC1.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:12][S:30]([C:24]3[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:23]=3[F:22])(=[O:32])=[O:31])=[CH:8][C:9]=2[CH3:11])[C:4]([CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:3]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 69431066HCID 69431066, compound

Product 1

HCID 10160063HCID 10160063, compoundYield 68.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1,7-dimethyl-3-(1-methylpiperdin-4-yl)-5-hydroxy-1H-indole (1.0 eq, 1.98 mmol, 0.511 g) in THF (5.0 mL) at room temperature was added 60% sodium hydride (1.2 eq, 2.37 mmol, 0.095 g). After stirring five minutes 2,6-difluorobenzenesulfonyl chloride (1.1 eq, 2.18 mmol, 0.384 g) was added. The reactions were stirred at room temperature for 3 hours. The reaction was treated with water (25 mL) and 1N sodium hydroxide (2 mL) then extracted with ethyl acetate (2×25 mL). The organic phases were combined, washed with water (25 mL) then brine (25 mL), dried over sodium sulfate, filtered and concentrated in vacuo to an oil. This material was subjected to radial chromatography, 4 mm plate, eluting with 9:1 chloroform:2M ammonia in methanol. Fractions containing product were combined, concentrated in vacuo to afford an oil. The title compound was crystallized from diethyl ether to afford 0.592 g (59%) of the title compound: mp=139° C.; Mass spectrum (ion spray): m/z=439 (M+1); 1H NMR (DMSOd6): 7.95-7.85 (m, 1H), 7.43-7.37 (m, 2H), 7.05 (s, 1H), 6.84 (d, J=2.20 Hz, 1H), 6.64 (d, J=1.46 Hz, 1H), 3.96 (s, 3H), 2.79 (m, 2H), 2.64 (s, 3H), 2.50-2.40 (m, 1H), 2.19 (s, 3H), 1.96 (m, 1H), 1.92 (m, 1H), 1.69-1.56 (m, 2H), 1.53 (m, 1H), 1.44 (m, 1H); Calculated for C22H26N2F2O3S: C, 60.89; H, 5.57; N, 6.45. Found: C, 60.67; H, 5.64; N, 6.54.

Workup

  1. additionwas added
  2. extractionthen extracted with ethyl acetate (2×25 mL)
  3. washwashed with water (25 mL)
  4. dry with materialbrine (25 mL), dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to an oil
  7. washeluting with 9:1 chloroform
  8. additionFractions containing product
  9. concentrationconcentrated in vacuo
  10. customto afford an oil
  11. customThe title compound was crystallized from diethyl ether

Sources & evidence

ORD record
ord-e2987c576d2e4e389d8d9ca8f85a79d1
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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