Potassium Carbonate → (R)-1-(1-(3-cyanophenyl)ethyl)-1H-indole-4,5-dicarbonitrile

HRID 1851139Notes

Reaction equation

HRID 1851139 reaction equation
F[C:2]1[C:3]([C:12]#[C:13][Si](C)(C)C)=[C:4]([C:10]#[N:11])[C:5](=[CH:8][CH:9]=1)[C:6]#[N:7].[NH2:18][C@@H:19]([C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[C:24]#[N:25])[CH3:20].C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1>[C:24]([C:23]1[CH:22]=[C:21]([C@H:19]([N:18]2[C:2]3[C:3](=[C:4]([C:10]#[N:11])[C:5]([C:6]#[N:7])=[CH:8][CH:9]=3)[CH:12]=[CH:13]2)[CH3:20])[CH:28]=[CH:27][CH:26]=1)#[N:25]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 21065209(R)-3-(1-aminoethyl)benzonitrileHCID 86709187HCID 86709187, compound

Product 1

HCID 86709196(R)-1-(1-(3-cyanophenyl)ethyl)-1H-indole-4,5-dicarbonitrileYield 45.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

An oven-dried vial was charged with 4-fluoro-3-((trimethylsilyl)ethynyl)phthalonitrile (Example 40C) (0.128 g, 0.528 mmol), (R)-3-(1-aminoethyl)benzonitrile (0.085 g, 0.581 mmol), and K2CO3 (0.080 g, 0.581 mmol) and sealed with a rubber septum. Anhyd NMP (3 mL) was added via syringe and the mixture was stirred in a heating block at 60° C. under N2. After 3.5 h the septum was replaced with a PTFE-faced crimp top and the mixture was subjected to microwave heating (140° C.) for 20 min. Upon cooling, the mixture was poured into satd NaHCO3 and extracted with EtOAc (×3). Combined organics were filtered (Whatman #2), washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution) affording (R)-1-(1-(3-cyanophenyl)ethyl)-1H-indole-4,5-dicarbonitrile (0.0705 g, 0.238 mmol, 45.0% yield) as a tan foam: 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J=3.4 Hz, 1H), 7.61 (dt, J=7.8, 1.3 Hz, 1H), 7.50-7.41 (m, 3H), 7.40 (t, J=1.8 Hz, 1H), 7.30-7.27 (m, 1H), 6.93 (dd, J=3.4, 0.7 Hz, 1H), 5.76 (q, J=7.1 Hz, 1H), 2.01 (d, J=7.1 Hz, 3H); MS (LCMS ES+) m/z 297 ([M+H]+, 24%), 338 ({[M+H]+MeCN}+, 100%).

Workup

  1. customsealed with a rubber septum
  2. temperatureheating (140° C.) for 20 min
  3. temperatureUpon cooling
  4. extractionextracted with EtOAc (×3)
  5. filtrationCombined organics were filtered (Whatman #2)
  6. washwashed (water, brine)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-e054b68bf5f945efb1b2b05dbe3e456a
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

Loading…