Water → 3,4,5,6-Tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid 2-fluoro-phenyl-amide

HRID 497396Notes

Reaction equation

HRID 497396 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].C[Al](C)C.C([O:15][C:16]([C:18]1[C:27]2[C:26]3[N:28]=[CH:29][N:30]=[CH:31][C:25]=3[CH2:24][CH2:23][CH2:22][C:21]=2[NH:20][CH:19]=1)=O)C.O>C(Cl)Cl.[NH4+].[Cl-]>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:16]([C:18]1[C:27]2[C:26]3[N:28]=[CH:29][N:30]=[CH:31][C:25]=3[CH2:24][CH2:23][CH2:22][C:21]=2[NH:20][CH:19]=1)=[O:15]

Participants

7

Reactant 4

HCID 962WaterHCID 95842-FluoroanilineHCID 16682925TrimethylaluminumHCID 206056153,4,5,6-Tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid ethyl ester

Product 1

HCID 206055933,4,5,6-Tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid 2-fluoro-phenyl-amideYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 2-fluoroaniline (108 mg, 0.972 mmol) in CH2Cl2 (2.0 mL) at 0° C. under N2 is slowly added AlMe3 (0.49 mL, 2.0 M in toluene). The resulting solution is stirred at room temperature for 1 h. Next, 3,4,5,6-tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid ethyl ester (50 mg, 0.194 mmol) is added in one portion. The resulting mixture is then stirred at reflux for 2 h. After cooling, the reaction mixture is carefully diluted with saturated aq NH4Cl (˜5 mL) and some H2O. The mixture is stirred vigorously for 15 min. and then extracted three times with CH2Cl2. The combined extracts are dried over K2CO3 and concentrated. The crude material is purified by flash chromatography on silica gel. Elution with 40:1 CHCl3—MeOH followed by 30:1 CHCl3—MeOH and finally 20:1 CHCl3—MeOH afforded 45 mg (72%) of 3,4,5,6-tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid (2-fluoro-phenyl)-amide as a light yellow solid. Electrospray mass spectrum: m/z 321 [M−1].

Workup

  1. customat 0° C.
  2. stirringThe resulting mixture is then stirred
  3. temperatureat reflux for 2 h
  4. temperatureAfter cooling
  5. stirringThe mixture is stirred vigorously for 15 min.
  6. extractionextracted three times with CH2Cl2
  7. dry with materialThe combined extracts are dried over K2CO3
  8. concentrationconcentrated
  9. customThe crude material is purified by flash chromatography on silica gel
  10. washElution with 40:1 CHCl3—MeOH

Sources & evidence

ORD record
ord-5e94b577676e4826b529eecf3e2836be
Source dataset
uspto-grants-2005_09
Patent number
US06949562B2

Reaction notes

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