3-Fluoroaniline → HCID 18766887, compound

HRID 481102Notes

Reaction equation

HRID 481102 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C[Al](C)C.C[O:14][C:15]([C:17]1[C:26]2[C:25]3[N:27]=[CH:28][CH:29]=[CH:30][C:24]=3[CH2:23][NH:22][CH2:21][C:20]=2[NH:19][CH:18]=1)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:15]([C:17]2[C:26]3[C:25]4[N:27]=[CH:28][CH:29]=[CH:30][C:24]=4[CH2:23][NH:22][CH2:21][C:20]=3[NH:19][CH:18]=2)=[O:14])[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 97423-FluoroanilineHCID 16682925TrimethylaluminumHCID 20605628HCID 20605628, compound

Product 1

HCID 18766887HCID 18766887, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 0.38 mL (4 mmol) of 3-fluoroaniline in 2 mL of methylene chloride under a nitrogen atmosphere is added dropwise 1.5 mL (3 mmol) of trimethyl aluminum (2M solution of toluene). This mixture is stirred at room temperature for 30 minutes. To this mixture is added a solution of 0.12 g (0.5 mmol) of 3,4,5,6-tetrahydro-3,5,10-triaza-benzo(e)azulene-1-carboxylic acid methyl ester dissolved in 8 mL of methylene chloride. The reaction mixture is heated to 40° C. for 24 hours; cooled to room temperature and quenched with 0.5 mL of saturated NaCl. After stirring for 30 minutes an additional 5 mL of methylene chloride and 2 grams of anhydrous sodium sulfate is added. The reaction mixture is filtered. The filtrate is evaporated and chromatographed on 10 grams of silica gel using 10/1/0.5 chloroform/methanol/ammonium hydroxide as the eluant. Appropriate fractions are combined and evaporated to 23 mg of 3,4,5,6-tetrahydro-3,5,10-triaza-benzo(e)azulene-1-carboxylic acid (3-fluoro-phenyl)-amide. 1H NMR (CD3OD) δ8.70 (m, 1H), 7.90 (m, 1H), 7.80 (m, 1H), 7.60 (s, 1H), 7.30 (m, 3H), 6.90 (m, 1H), 3.87 (s, 2H), 3.70 (s, 2H). Mass spectrum: m/e=323.2 (p+1). TLC (10/1/0.1 chloroform/methanol/ammonium hydroxide) Rf=0.3.

Workup

  1. temperatureThe reaction mixture is heated to 40° C. for 24 hours
  2. temperaturecooled to room temperature
  3. customquenched with 0.5 mL of saturated NaCl
  4. stirringAfter stirring for 30 minutes an additional 5 mL of methylene chloride and 2 grams of anhydrous sodium sulfate
  5. additionis added
  6. filtrationThe reaction mixture is filtered
  7. customThe filtrate is evaporated
  8. customchromatographed on 10 grams of silica gel using 10/1/0.5 chloroform/methanol/ammonium hydroxide as the eluant
  9. customevaporated to 23 mg of 3,4,5,6-tetrahydro-3,5,10-triaza-benzo(e)azulene-1-carboxylic acid (3-fluoro-phenyl)-amide

Sources & evidence

ORD record
ord-1d710dcaa20a4c0981a3c6b62f7c30d5
Source dataset
uspto-grants-2003_11
Patent number
US06653471B2

Reaction notes

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