Cycloheptylamine → HCID 21897116, compound

HRID 2056670Notes

Reaction equation

HRID 2056670 reaction equation
[N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1Cl.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=1[Cl:25])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(C(C)C)CC)(C)C.[CH:35]1([NH2:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.[CH3:43][N:44]1[CH2:49][CH2:48][CH:47]([NH:50]C)[CH2:46][CH2:45]1>C(#N)C>[OH-:17].[NH4+:1].[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:2]2[N:4]=[C:5]([NH:42][CH:35]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[N:7]=[C:8]([NH:50][CH:47]3[CH2:48][CH2:49][N:44]([CH3:43])[CH2:45][CH2:46]3)[N:1]=2)=[CH:20][C:19]=1[Cl:25])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 5

HCID 2899CycloheptylamineHCID 7954Cyanuric chlorideHCID 81531Diisopropylethylamine3×HCID 5663231-Methyl-4-(methylamino)piperidineHCID 12682854-Benzyloxy-3-chloroaniline

Product 2

HCID 14923Ammonium HydroxideHCID 21897116HCID 21897116, compoundYield 13.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Conditions

Temperature
-20 °C

Procedure

To cyanuric chloride (3.148 g, 17.0 mmol) dissolved in acetonitrile (70 mL) stirring at −20° C., was added a solution of 4-benzyloxy-3-chloro-phenylamine (4.0188 g, 17.0 mmol) in acetonitrile (40 mL) followed by the addition of diisopropylethylamine (DIEA) (3 mL, 17.0 mmol), and was stirred at −20° C. for 1 hour under a nitrogen atmosphere. The mixture was allowed to warm to room temperature and then cycloheptylamine (2.2 mL, 17.0 mmol) was added in anhydrous acetonitrile (5 mL) followed by addition of a DIEA (3.2 mL, 18.7 mmol), and the mixture was stirred at room temperature overnight. To this reaction mixture was added DIEA (3.2 mL, 18.7 mmol) followed by addition of N-methyl-4-(methylamino)piperidine (2.5 mL, 17.0 mmol) and was stirred and heated at reflux overnight. The reaction mixture was extracted 3 times with methylene chloride; the combined organic layers were washed one time with brine and dried over anhydrous potassium carbonate. The organic layer was concentrated in vacuo and dried overnight under vacuum. Column chromatography (90:9:1 v:v:v dichloromethane:methanol:ammonium hydroxide) yielded E2 (619 mg, 7%); mp 84° C.; HPLC:Inertsil ODS 3V C18, 40:30:30 [KH2PO4(0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 37.1 min, 99.4% purity; MS (TOF ES+) m/z 550 (M+H, 100), 276 (M+2H, 34.9), 275.5 (83.9).

Workup

  1. stirringwas stirred at −20° C. for 1 hour under a nitrogen atmosphere
  2. temperatureto warm to room temperature
  3. stirringthe mixture was stirred at room temperature overnight
  4. stirringwas stirred
  5. temperatureheated
  6. temperatureat reflux overnight
  7. extractionThe reaction mixture was extracted 3 times with methylene chloride
  8. washthe combined organic layers were washed one time with brine
  9. dry with materialdried over anhydrous potassium carbonate
  10. concentrationThe organic layer was concentrated in vacuo
  11. customdried overnight under vacuum

Sources & evidence

ORD record
ord-9cb676c67d4840419f3cb650b50269ad
Source dataset
uspto-grants-2008_02
Patent number
US07335656B2

Reaction notes

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