Dimethylformamide → HCID 121268887, compound

HRID 2199614Notes

Reaction equation

HRID 2199614 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=4)=[O:19])=[CH:16][C:10]=3[CH:9]=2)=[CH:6][C:5]([N+]#[C-])=[CH:4][N:3]=1.[Cl-].[NH4+].[N-:36]=[N+:37]=[N-:38].[Na+].OS([O-])(=O)=O.[K+].[CH3:46][N:47](C)C=O>C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=4)=[O:19])=[CH:16][C:10]=3[CH:9]=2)=[CH:6][C:5]([C:46]2[N:36]=[N:37][NH:38][N:47]=2)=[CH:4][N:3]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium Chloride3×HCID 33557Sodium Azide2×HCID 516920Potassium bisulfateHCID 131735689HCID 131735689, compound

Product 1

HCID 121268887HCID 121268887, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of 1-(2-(2-amino-5-isocyanopyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1.3 g, 2.67 mmol, 1 eq), ammonium chloride (286 mg, 2 eq), and sodium azide (347 mg, 2 eq) in anhydrous dimethylformamide (8 mL) under nitrogen atmosphere was stirred and heated at 120° C. for 2 hours. The mixture was then cooled to room temperature and additional ammonium chloride (286 mg, 2 eq) and sodium azide (347 mg, 2 eq) were added. The reaction mixture was heated back to 120° C. and stirred at that temperature for another hour. After it was cooled to room temperature, it was transferred into a mixture of ethyl acetate and aqueous ammonium chloride; during the process, the pH of the aqueous layer was adjusted to 3˜4ish by using aq KHSO4 (10%). The organic layer was isolated, washed once with saturated brine, and dried with anhydrous sodium sulfate. The upper solution was decanted and concentrated down with silica gel. Upon gradient column chromatography (from EtOAc to MeOH-EtOAc 1:2), 1-{2-[2-amino-5-(2H-tetrazol-5-yl)pyridin-3-yl]-1-benzothien-5-yl}-3-[4-chloro-3-(trifluoromethyl)phenyl]urea was obtained as a yellow solid in the amount of 452 mg.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. temperatureThe reaction mixture was heated back to 120° C.
  3. stirringstirred at that temperature for another hour
  4. temperatureAfter it was cooled to room temperature
  5. customThe organic layer was isolated
  6. washwashed once with saturated brine
  7. dry with materialdried with anhydrous sodium sulfate
  8. customThe upper solution was decanted
  9. concentrationconcentrated down with silica gel

Sources & evidence

ORD record
ord-1e0eb685ed874f34875e315c9e8e0d4e
Source dataset
uspto-grants-2016_06
Patent number
US09359336B2

Reaction notes

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