Hydrochloric Acid → HCID 178433614, compound

HRID 1405302Notes

Reaction equation

HRID 1405302 reaction equation
[CH3:1][N:2]([CH:31]([CH3:33])[CH3:32])[C:3]1[C:4]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19]([CH3:24])=[C:18]3[C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([C:13]#[N:14])=[CH:8][CH:7]=2.[N-:34]=[N+:35]=[N-:36].[Na+].Cl>CS(C)=O.O.[Zn+2].[Br-].[Br-]>[F:28][C:26]([F:29])([F:27])[C:25]([C:18]1[C:17]2[C:21](=[CH:22][CH:23]=[C:15]([C:4]3[C:3]([N:2]([CH:31]([CH3:33])[CH3:32])[CH3:1])=[N:12][C:11]4[C:6](=[CH:7][CH:8]=[C:9]([C:13]5[NH:36][N:35]=[N:34][N:14]=5)[CH:10]=4)[N:5]=3)[CH:16]=2)[NH:20][C:19]=1[CH3:24])=[O:30]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 70654214HCID 70654214, compound

Product 1

HCID 178433614HCID 178433614, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

To a solution of 3-[methyl(propan-2-yl)amino]-2-[2-methyl-3-(2,2,2-trifluoroacetyl)-1H-indol-5-yl]quinoxaline-6-carbonitrile (160 mg, 0.35 mmol) in DMSO (20 ml) was added ZnBr2 (38 mg, 0.17 mmol) and NaN3 (91 mg, 1.40 mmol) in water (2 ml). The resulting solution was heated to reflux overnight and diluted with water (200 ml), adjusted to pH 3 with HCl (2N), extracted with ethyl acetate (5×50 ml), and the organic layers combined and dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (15% dichloromethane in methanol) to afford 2,2,2-trifluoro-1-(5-(3-(isopropyl(methyl)amino)-6-(1H-tetrazol-5-yl)quinoxalin-2-yl)-2-methyl-1H-indol-3-yl)ethanone as a yellow solid (38.6 mg, 27%).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux overnight
  3. extractionextracted with ethyl acetate (5×50 ml)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a residue, which
  7. customwas purified by silica gel column chromatography (15% dichloromethane in methanol)

Sources & evidence

ORD record
ord-d31392b9ae294249801e1d77f8cf48b5
Source dataset
uspto-grants-2014_12
Patent number
US08916561B2

Reaction notes

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