Ethyl formate → HCID 44466107, compound

HRID 241617Notes

Reaction equation

HRID 241617 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[C:9]3[C:14]([C:15]=2/[C:16](=[N:18]/[OH:19])/[NH2:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1.[H-].[Na+].[CH:30](OCC)=O>C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=3)[C:9]3[C:14]([C:15]=2[C:16]2[N:17]=[CH:30][O:19][N:18]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 58378199HCID 58378199, compound

Product 1

HCID 44466107HCID 44466107, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(Z)-2-(3,5-Dimethylisoxazol-4-yl)-N-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3 carboximidamide (Example 11) was dissolved in THF containing 4-Å powdered molecular sieves. The mixture was stirred for 30 min under N2. NaH (60% dispersion in mineral oil, 7.0 mg, 2.1 eq.) was added and the mixture was stirred at 60° C. for 20 min. After cooling to room temperature, ethyl formate (25.6 mg, 2.5 eq) in THF was added dropwise. The resulting mixture was heated at reflux for 1 h and then cooled to room temperature. The mixture was filtered and concentrated. The residue was filtered through silica and then purified using reversed phase HPLC to give 4-(2-(3,5-dimethylisoxazol-4-yl)-3-(1,2,4-oxadiazol-3-yl)-1H-indol-1-yl)phenol as a white powder: ES/MS m/z; 395.17 (M+H), 393.19 (M−H); NMR (acetone-d6, 500 MHz): 9.21 (s, 1H), 8.40 (m, 1H), 7.37-7.31 (m, 2H), 7.26-7.22 (m, 3H), 6.98 (m, 2H), 2.17 (s, 3H) and 1.98 (s, 3H).

Workup

  1. stirringthe mixture was stirred at 60° C. for 20 min
  2. temperatureThe resulting mixture was heated
  3. temperatureat reflux for 1 h
  4. temperaturecooled to room temperature
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated
  7. filtrationThe residue was filtered through silica
  8. custompurified

Sources & evidence

ORD record
ord-d9897e42731f4d86bf73ed6bf4b48723
Source dataset
uspto-grants-2014_02
Patent number
US08653072B2

Reaction notes

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