Pyridine → N-(1-{3-[(R)-2-[3-(phenylsulphonylamino)-phenyl]-2-hydroxy-ethylamino]-3-methyl-butyl}-1H-indol-5-yl)-oxalamidic acid

HRID 2355256Notes

Reaction equation

HRID 2355256 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][C:13]([NH:16][CH2:17][C@@H:18]([C:20]1[CH:21]=[C:22]([NH:26][S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:29])=[O:28])[CH:23]=[CH:24][CH:25]=1)[OH:19])([CH3:15])[CH3:14])[CH:6]=[CH:5]2.N1C=CC=CC=1.[Cl-].[C:43](OC)(=[O:47])[C:44]([O-:46])=[O:45].[OH-].[Na+].C(O)(C(F)(F)F)=O>C1COCC1.CO>[C:30]1([S:27]([NH:26][C:22]2[CH:21]=[C:20]([C@@H:18]([OH:19])[CH2:17][NH:16][C:13]([CH3:14])([CH3:15])[CH2:12][CH2:11][N:7]3[C:8]4[C:4](=[CH:3][C:2]([NH:1][C:43](=[O:47])[C:44]([OH:46])=[O:45])=[CH:10][CH:9]=4)[CH:5]=[CH:6]3)[CH:25]=[CH:24][CH:23]=2)(=[O:29])=[O:28])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 22574234Monomethyl oxalate chlorideHCID 58875109N-(3-{(R)-2-[3-(5-amino-indol-1-yl)-1,1-dimethyl-propylamino]-1-hydroxy-ethyl}-phenyl)-benzenesulphonamide2×

Product 1

HCID 58875124N-(1-{3-[(R)-2-[3-(phenylsulphonylamino)-phenyl]-2-hydroxy-ethylamino]-3-methyl-butyl}-1H-indol-5-yl)-oxalamidic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The free base of N-(3-{(R)-2-[3-(5-amino-indol-1-yl)-1,1-dimethyl-propylamino]-1-hydroxy-ethyl}-phenyl)-benzenesulphonamide-hydrotrifluoroacetate (free base from Example 20; 100 mg, 0.20 mmol) and pyridine (33 μl, 0.41 mmol) are dissolved in 3 ml THF. At 0° C. methyl oxalate chloride (21 μl, 0.22 mmol) is added and the reaction mixture is stirred for 3 hours at RT. The solvent is eliminated in vacuo and the residue is dissolved in 3 ml of methanol. Sodium hydroxide solution (4N; 1.5 ml) is added dropwise to the mixture. Then the reaction mixture is stirred for 18 hours at RT and then acidified with TFA. The solution is chromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0].

Workup

  1. stirringThen the reaction mixture is stirred for 18 hours at RT
  2. customThe solution is chromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0]

Sources & evidence

ORD record
ord-74c080a6d57c409c910a32ad250b760a
Source dataset
uspto-grants-2010_07
Patent number
US07754756B2

Reaction notes

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