Acetic Acid → 3-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-{[(2-dimethylamino-ethyl)-methyl-amino]-methyl}-benzoyloxymethyl ester dihydrochloride salt

HRID 1384509Notes

Reaction equation

HRID 1384509 reaction equation
[CH:1]([C:3]1[CH:52]=[CH:51][C:6]([C:7]([O:9][CH2:10][O:11][C:12]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([CH2:23][C:24]([NH:37][C:38]([O:40][CH2:41][C:42]3[O:43][C:44]4[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=4[CH:46]=3)=[O:39])([C:26](=[O:36])[NH:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:29])[CH3:25])=[CH:15]2)=[O:13])=[O:8])=[CH:5][CH:4]=1)=O.[CH3:53][N:54]([CH3:59])[CH2:55][CH2:56][NH:57][CH3:58].C(O)(=O)C.C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:70]>>[ClH:70].[ClH:70].[CH3:53][N:54]([CH3:59])[CH2:55][CH2:56][N:57]([CH2:1][C:3]1[CH:4]=[CH:5][C:6]([C:7]([O:9][CH2:10][O:11][C:12]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([CH2:23][C:24]([NH:37][C:38]([O:40][CH2:41][C:42]3[O:43][C:44]4[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=4[CH:46]=3)=[O:39])([C:26](=[O:36])[NH:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH3:29])[CH3:25])=[CH:15]2)=[O:13])=[O:8])=[CH:51][CH:52]=1)[CH3:58]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6212ChloroformHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 516892Sodium BicarbonateHCID 206699173-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-formylbenzoyloxymethyl ester

Product 1

HCID 702446883-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-{[(2-dimethylamino-ethyl)-methyl-amino]-methyl}-benzoyloxymethyl ester dihydrochloride saltYield 84%

Procedure

NaHB(OAc)3 (0.21 g, 1.0 mmol, 1.4 eq.) was added in three equal portions in 10 minutes to a cloudy solution of compound 19 (0.5 g, 0.713 mmol), N,N,N′-trimethylethylenediamine (0.316 mL, 1.07 mmol, 1.5 eq.) and acetic acid (0.061 mL, 1.07 mmol, 1.5 eq.) in dry chloroform (20 mL) under N2 in an ice bath. The reaction was stirred in ice bath for 30 minutes and room temperature for 20 hours to give a white suspension. Saturated sodium bicarbonate (20 mL) was added to the reaction mixture and stirred for 30 minutes. The organic layer was washed with saturated sodium bicarbonate (30 mL), saturated sodium chloride and dried over anhydrous sodium sulfate. The product was further purified by silica gel chromatography (2.5×6 cm) eluting with CHCl3/MeOH (10:0.5) to give compound 20f as a white foam (0.47 g, 84%).

Workup

  1. customroom temperature for 20 hours to give a white suspension
  2. stirringstirred for 30 minutes
  3. washThe organic layer was washed with saturated sodium bicarbonate (30 mL), saturated sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe product was further purified by silica gel chromatography (2.5×6 cm)
  6. washeluting with CHCl3/MeOH (10:0.5)

Sources & evidence

ORD record
ord-d0691da78442489e9dd5bc7e4dd21157
Source dataset
uspto-grants-2001_07
Patent number
US06258800B1

Reaction notes

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