Potassium Carbonate → (S)-1-(3-hydroxy-3-methylbutan-2-yl)-1H-indole-4,5-dicarbonitrile

HRID 1851130Notes

Reaction equation

HRID 1851130 reaction equation
[NH2:1][C@@H:2]([CH3:7])[C:3]([CH3:6])([OH:5])[CH3:4].F[C:9]1[C:10]([C:19]#[C:20][Si](C)(C)C)=[C:11]([C:17]#[N:18])[C:12](=[CH:15][CH:16]=1)[C:13]#[N:14].C([O-])([O-])=O.[K+].[K+].CN1C(=O)CCC1>O>[OH:5][C:3]([CH3:6])([CH3:4])[C@@H:2]([N:1]1[C:9]2[C:10](=[C:11]([C:17]#[N:18])[C:12]([C:13]#[N:14])=[CH:15][CH:16]=2)[CH:19]=[CH:20]1)[CH3:7]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 51415372(S)-3-Amino-2-methylbutan-2-OLHCID 86709187HCID 86709187, compound

Product 1

HCID 86709186(S)-1-(3-hydroxy-3-methylbutan-2-yl)-1H-indole-4,5-dicarbonitrileYield 50.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

An oven-dried vial was charged with (S)-3-amino-2-methylbutan-2-ol (Example 21G) (0.064 g, 0.622 mmol), 4-fluoro-3-((trimethylsilyl)ethynyl)phthalonitrile (0.126 g, 0.518 mmol), and K2CO3 (0.143 g, 1.036 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 30 min, the vial was sealed with a PTFE-faced crimp top and the mixture was subjected to microwave heating (140° C.) for 15 min. The mixture was poured into water and extracted with EtOAc (×3). 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) affording (S)-1-(3-hydroxy-3-methylbutan-2-yl)-1H-indole-4,5-dicarbonitrile (0.0659 g, 50% yield) as a tan solid: 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J=8.7 Hz, 1H), 7.69 (d, J=3.3 Hz, 1H), 7.51 (d, J=8.7 Hz, 1H), 6.84 (d, J=3.2 Hz, 1H), 4.47 (q, J=7.0 Hz, 1H), 1.63 (d, J=7.0 Hz, 3H), 1.53 (s, 1H), 1.34 (s, 3H), 1.11 (s, 3H).

Workup

  1. customsealed with a rubber septum
  2. temperatureheating (140° C.) for 15 min
  3. extractionextracted with EtOAc (×3)
  4. washCombined organics were washed (water, brine)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-4a4b8b1863bb4750916c2168f13ea706
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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