Sodium hydride → [2-(3-Chloro-5-{isopropyl-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-carbamoyl}-phenoxy)-ethyl]-pyridin-4-yl-carbamic acid tert-butyl ester

HRID 2268602Notes

Reaction equation

HRID 2268602 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([OH:22])[CH:21]=1)[C:5]([N:7]([CH:16]([CH3:18])[CH3:17])[CH2:8][CH2:9][C:10]1[N:14]([CH3:15])[N:13]=[N:12][N:11]=1)=[O:6].[H-].[Na+].[C:25]([O:29][C:30]([N:32]([C:46]1[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=1)[CH2:33][CH2:34]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:31])([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C>[C:25]([O:29][C:30](=[O:31])[N:32]([CH2:33][CH2:34][O:22][C:20]1[CH:19]=[C:4]([C:5](=[O:6])[N:7]([CH:16]([CH3:17])[CH3:18])[CH2:8][CH2:9][C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:3]=[C:2]([Cl:1])[CH:21]=1)[C:46]1[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=1)([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 183488353-Chloro-5-hydroxy-N-isopropyl-N-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-benzamideHCID 54393691Toluene-4-sulfonic acid 2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethyl ester

Product 1

HCID 54506817[2-(3-Chloro-5-{isopropyl-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-carbamoyl}-phenoxy)-ethyl]-pyridin-4-yl-carbamic acid tert-butyl esterYield 23.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chloro-5-hydroxy-N-isopropyl-N-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-benzamide (0.070 g) in DMF (2.0 ml) stirred at room temperature under nitrogen was added sodium hydride (60% dispersion in oil, 0.010 g) and after 10 min was added toluene-4-sulfonic acid 2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethyl ester (0.120 g). The reaction was stirred for 88 h and the sovent removed in vacuo. The residue was partitioned between ethyl acetate and water. The organic phase was washed with further water and 1M aqueous sodium hydroxide, water and dried with brine and over sodium sulphate and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography, eluting with ethyl acetate:petroleum ether (4:1 v/v) and 24:1 dichloromethane:methanol (24:1 v/v), to give the title compound as a colourless gum (0.028 g).

Workup

  1. customthe sovent removed in vacuo
  2. customThe residue was partitioned between ethyl acetate and water
  3. washThe organic phase was washed with further water and 1M aqueous sodium hydroxide, water
  4. dry with materialdried with brine and over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash column chromatography
  8. washeluting with ethyl acetate:petroleum ether (4:1 v/v) and 24:1 dichloromethane:methanol (24:1 v/v)

Sources & evidence

ORD record
ord-f6288c02baa14fa9a4cd052ebd822be9
Source dataset
uspto-grants-2001_12
Patent number
US06326386B1

Reaction notes

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