Hydrochloric Acid → 2-(4-{[bis(1H-imidazol-2-ylmethyl)amino]methyl}benzyl)-2,8-diazaspiro[4.5]decan-3-one

HRID 1920139Notes

Reaction equation

HRID 1920139 reaction equation
Cl.CN(C)S([N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][N:13]([CH2:26][C:27]1[CH:51]=[CH:50][C:30]([CH2:31][N:32]2[C:36](=[O:37])[CH2:35][C:34]3([CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38]3)[CH2:33]2)=[CH:29][CH:28]=1)[CH2:14][C:15]1[N:16](S(N(C)C)(=O)=O)[CH:17]=[CH:18][N:19]=1)(=O)=O.[OH-].[Na+]>>[NH:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][N:13]([CH2:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:31][N:32]2[C:36](=[O:37])[CH2:35][C:34]3([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)[CH2:33]2)=[CH:50][CH:51]=1)[CH2:14][C:15]1[NH:19][CH:18]=[CH:17][N:16]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67502412tert-butyl 2-(4-{[bis({1-[(dimethylamino)sulfonyl]-1H-imidazol-2-yl}methyl)amino]methyl}benzyl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 675021312-(4-{[bis(1H-imidazol-2-ylmethyl)amino]methyl}benzyl)-2,8-diazaspiro[4.5]decan-3-oneYield 99.6%

Procedure

A 2N-hydrochloric acid (5 mL) solution of the compound (480 mg) obtained in Example 45 was stirred at 80° C. for 3 hours. After the reaction solution was cooled to room temperature, the pH was adjusted to 12 with an aqueous 2N-sodium hydroxide solution. The aqueous layer was extracted four times with dichloromethane. The combined organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate:10%-saturated aqueous ammonia-methanol=1:0→7:3) to obtain the title compound (277 mg) having the following physical properties.

Workup

  1. extractionThe aqueous layer was extracted four times with dichloromethane
  2. washThe combined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter removing the anhydrous magnesium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (ethyl acetate:10%-saturated aqueous ammonia-methanol=1:0→7:3)

Sources & evidence

ORD record
ord-5a7b2badb7ac40918f59b166e5616096
Source dataset
uspto-grants-2012_05
Patent number
US08168783B2

Reaction notes

Loading…