Cycloheptylamine → HCID 10049778, compound

HRID 915133Notes

Reaction equation

HRID 915133 reaction equation
[N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1Cl.C([N:13](CC)[CH:14]([CH3:16])[CH3:15])(C)C.[F:19][C:20]1C=C(C=[CH:26][C:27]=1N)OC.[CH:29]1([NH2:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.[CH3:37][N:38]1[CH2:43][CH2:42][CH:41]([NH:44][CH3:45])[CH2:40][CH2:39]1.[C:46](=[O:49])(O)[O-].[Na+]>O1CCOCC1.CC#N.[Cl-].[Na+].O>[CH:29]1([NH:36][C:2]2[N:4]=[C:5]([NH:13][C:14]3[CH:15]=[CH:26][C:27]([O:49][CH3:46])=[C:20]([F:19])[CH:16]=3)[N:7]=[C:8]([N:44]([CH3:45])[CH:41]3[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]3)[N:1]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

10

Reactant 6

HCID 2899CycloheptylamineHCID 7954Cyanuric chlorideHCID 81531Diisopropylethylamine3×HCID 516892Sodium BicarbonateHCID 5663231-Methyl-4-(methylamino)piperidineHCID 37563832-Fluoro-4-methoxyaniline

Product 1

HCID 10049778HCID 10049778, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent4×HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To cyanuric chloride (0.180 g, 1 mmol) in 1,4-dioxane (1 mL) at about −10 to −20° C. was added N,N-diisopropylethylamine (DIEA) (0.19 mL, 1 mmol) in CH3CN (1 mL) and 3-fluoro-p-anisidine (0.14 g, 1 mmol) in CH3CN (1 mL) and stirred for about 1 hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then a solution of cycloheptylamine (0.13 mL, 1 mmol) and DIEA (0.19 mL, 1 mmol) in CH3CN (0.5 mL) was added and the reaction mixture was stirred overnight at rt. Then, N-methyl-4(methylamino)piperidine (0.15 mL, 1 mmol) and DIEA (0.19 mL, 1 mmol) in CH3CN (0.5 mL) were added and the reaction mixture was refluxed overnight. The reaction mixture was worked-up using saturated sodium bicarbonate, and brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane:methanol:conc. ammonium hydroxide) to give 158 (0.130 g, 28%); TLC (silica gel, 90:9:1, CH2Cl2, CH3OH, conc. NH4OH), Rf 0.26); 1H NMR (600 MHz, CDCl3, 55° C.) δ 7.74 (br s, 1H), 6.94 (br s, 1H), 6.81-6.84 (m, 2H), 4.83 (br resonance, 1H), 4.55 (s, 1H), 3.98 (s, 1H), 3.82 (s, 3H), 2.97 (s, 3H), 2.94 (br d, J=11.9 Hz, 2H), 2.29 (s, 3H), 2.06-2.10 (m, 2H), 1.93-1.97 (m, 2H), 1.84-1.90 (m, 2H), 1.44-1.66 (m, 12H).

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for about 1 hour
  2. stirringthe reaction mixture was stirred overnight at rt
  3. temperaturethe reaction mixture was refluxed overnight
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane:methanol:conc. ammonium hydroxide)

Sources & evidence

ORD record
ord-a97e0167dcbb4c57a8bea3ba65075751
Source dataset
uspto-grants-2007_09
Patent number
US07265114B2

Reaction notes

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