Water → 2-(6-chloro-9-(3-hydroxy-3-methylbut-1-ynyl)-1H-phenanthro[9,10-d]imidazol-2-yl)isophthalonitrile

HRID 549484Notes

Reaction equation

HRID 549484 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:26](=[CH:27][CH:28]=1)[C:12]1[NH:13][C:14]([C:16]3[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[CH:20][C:17]=3[C:18]#[N:19])=[N:15][C:11]=1[C:10]1[CH:9]=[CH:8][C:7]([Cl:29])=[CH:6][C:5]2=1.[CH3:30][C:31]([OH:35])([C:33]#[CH:34])[CH3:32].C(NC(C)C)(C)C.O>CN(C=O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[Cl:29][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[C:11]1[NH:15][C:14]([C:16]3[C:17]([C:18]#[N:19])=[CH:20][CH:21]=[CH:22][C:23]=3[C:24]#[N:25])=[N:13][C:12]=1[C:26]1[CH:27]=[CH:28][C:2]([C:34]#[C:33][C:31]([OH:35])([CH3:32])[CH3:30])=[CH:3][C:4]2=1

Participants

9

Reactant 4

HCID 962WaterHCID 7912DiisopropylamineHCID 82582-Methyl-3-butyn-2-olHCID 178509773HCID 178509773, compound

Product 1

HCID 1784590322-(6-chloro-9-(3-hydroxy-3-methylbut-1-ynyl)-1H-phenanthro[9,10-d]imidazol-2-yl)isophthalonitrile

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 13 g of 2-(9-bromo-6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)isophthalonitrile in 240 mL of DMF is added 5.5 mL of 2-methyl-3-butyn-2-ol, 2.0 g of tetrakis(triphenylphosphine)palladium, 1.1 g of copper iodide and 5.6 mL of diisopropylamine. The mixture is stirred at 55° C. for 1 hr then cooled to room temperature and diluted with ethyl acetate (250 mL). Water (250 mL) is added and the layers were separated, the organic phase is washed with brine, dried over magnesium sulphate and volatiles are removed under reduced pressure. The crude mixture is then purified on silica gel using 50% hexane/ethyl acetate. The product is then recrystallized in THF and triturated in hot ethyl acetate/ether mixture to afford 5.4 g of [9-chloro-6-(3-hydroxy-3-methylbut-1-yn-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl]isophthalonitrile as a light yellow solid. 1H NMR (Acetone-d6): 8.93 (s, 2H), 8.53 (m, 2H), 8.36 (d, 2H), 8.01 (t, 1H), 7.78 (d, 2H), 4.53 (s, 1H), 1.61 (s, 6H).

Workup

  1. temperaturethen cooled to room temperature
  2. customthe layers were separated
  3. washthe organic phase is washed with brine
  4. dry with materialdried over magnesium sulphate and volatiles
  5. customare removed under reduced pressure
  6. customThe crude mixture is then purified on silica gel using 50% hexane/ethyl acetate
  7. customThe product is then recrystallized in THF
  8. customtriturated in hot ethyl acetate/ether mixture

Sources & evidence

ORD record
ord-972da15fb61849e495ee922ec6f032cc
Source dataset
uspto-grants-2011_05
Patent number
US07943649B2

Reaction notes

Loading…