Sodium Bicarbonate → 4-Methoxy-2,6-dimethyl-N-((1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)methyl)benzenesulfonamide

HRID 453920Notes

Reaction equation

HRID 453920 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[N:10]([CH2:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]3([CH2:25][CH2:24][N:23]([C:26]4[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=4)[CH2:22][CH2:21]3)[CH2:17][CH2:16]1)=[O:14])[CH:9]=[CH:8]2.C([O-])(O)=O.[Na+].[CH3:37][C:38]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[C:40]([CH3:46])[C:39]=1[S:47](Cl)(=[O:49])=[O:48]>C1COCC1.O.C1COCC1.O>[CH3:45][O:44][C:42]1[CH:43]=[C:38]([CH3:37])[C:39]([S:47]([NH:1][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[C:7]3[C:11]=2[N:10]([CH2:12][C:13](=[O:14])[N:15]2[CH2:20][CH2:19][C:18]4([CH2:21][CH2:22][N:23]([C:26]5[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=5)[CH2:24][CH2:25]4)[CH2:17][CH2:16]2)[CH:9]=[CH:8]3)(=[O:48])=[O:49])=[C:40]([CH3:46])[CH:41]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 159174964-Methoxy-2,6-dimethylbenzene-1-sulfonyl chlorideHCID 594736752-(7-(aminomethyl)-1H-indol-1-yl)-1-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethanone

Product 1

HCID 468969494-Methoxy-2,6-dimethyl-N-((1-(2-oxo-2-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethyl)-1H-indol-7-yl)methyl)benzenesulfonamideYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

A mixture of 2-(7-(aminomethyl)-1H-indol-1-yl)-1-(9-(pyridin-4-yl)-3,9-diazaspiro-[5.5]undecan-3-yl)ethanone (220 mg, 0.53 mmol, 1.0 equiv.) and NaHCO3 (134 mg, 1.59 mmol, 3.0 equiv.) in THF-water(1:1, 20 ml) was added at 0° C. to a solution of 2,6-dimethyl-4-methoxyphenylsulfonyl chloride (136 mg, 0.58 mmol, 1.1 equiv.) in THF (5 ml), and the mixture was stirred for 16 h at RT. The reaction mixture was diluted with water (15 ml) and extracted with ethyl acetate (3×30 ml). The combined organic phases were washed with sat. NaCl solution (40 ml) and dried over Na2SO4. The solvent was removed under vacuum and the crude product was purified by column chromatography (silica gel; 6-8% MeOH/DCM), and the desired product was thus obtained in the form of a white solid.

Workup

  1. extractionextracted with ethyl acetate (3×30 ml)
  2. washThe combined organic phases were washed with sat. NaCl solution (40 ml)
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed under vacuum
  5. customthe crude product was purified by column chromatography (silica gel; 6-8% MeOH/DCM)

Sources & evidence

ORD record
ord-006d998348344de28b4803f8c76b3f2b
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

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