Potassium Carbonate → HCID 86709188, compound

HRID 1851131Notes

Reaction equation

HRID 1851131 reaction equation
[NH2:1][CH:2]([CH2:7][CH3:8])[C:3]([CH3:6])([OH:5])[CH3:4].F[C:10]1[C:11]([C:20]#[C:21][Si](C)(C)C)=[C:12]([C:18]#[N:19])[C:13](=[CH:16][CH:17]=1)[C:14]#[N:15].C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CCOC(C)=O.CN1C(=O)CCC1>[OH:5][C:3]([CH3:6])([CH:2]([N:1]1[C:10]2[C:11](=[C:12]([C:18]#[N:19])[C:13]([C:14]#[N:15])=[CH:16][CH:17]=2)[CH:20]=[CH:21]1)[CH2:7][CH3:8])[CH3:4]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 203234723-Amino-2-methylpentan-2-olHCID 86709187HCID 86709187, compound

Product 1

HCID 86709188HCID 86709188, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

An oven-dried 20 mL microwave vial was charged with 3-amino-2-methylpentan-2-ol (Example 34A) (0.0705 g, 0.602 mmol), 4-fluoro-3-((trimethylsilyl)ethynyl)phthalonitrile (Example 40C) (0.146 g, 0.602 mmol), and K2CO3 (0.100 g, 0.722 mmol). Anhyd NMP (3 mL) was added via syringe and the vial was sealed with a PTFE-faced crimp top. The mixture was subjected to microwave heating (140° C.) for 35 min. The mixture was cooled, poured into satd NaHCO3, layered with EtOAc and the whole was filtered (Whatman #2). Layers were separated and the aqueous layer was extracted with EtOAc (×2). Combined organics were 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). Fractions containing the desired product were decolorized with activated carbon affording 1-(2-hydroxy-2-methylpentan-3-yl)-1H-indole-4,5-dicarbonitrile (0.0285 g, 18% yield) as an amber film: 1H NMR (400 MHz, CDCl3) δ 7.75-7.61 (m, 2H), 7.53 (d, J=8.6 Hz, 1H), 6.88 (d, J=3.3 Hz, 1H), 4.16-4.07 (m, 1H), 2.20-2.01 (m, 2H), 1.37 (s, 3H), 1.08 (s, 3H), 0.65 (t, J=7.3 Hz, 3H); MS (LCMS ES+) m/z 268 ([M+H]+, 26%), 285 (100%), 309 ({[M+H]+MeCN}+, 78%).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationthe whole was filtered (Whatman #2)
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (×2)
  5. washCombined organics were washed (water, brine)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)
  9. additionFractions containing the desired product

Sources & evidence

ORD record
ord-979ce4e07e924486b85fc5b2df807f17
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

Loading…