Diisopropylamine → HCID 178458164, compound

HRID 549488Notes

Reaction equation

HRID 549488 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:18]3[N:17]=[C:16]([C:19]4[C:26]([C:27]#[N:28])=[CH:25][CH:24]=[CH:23][C:20]=4[C:21]#[N:22])[NH:15][C:14]=3[C:13]3[C:8](=[CH:9][C:10]([C:29]([OH:32])([CH3:31])[CH3:30])=[CH:11][CH:12]=3)[C:6]=2[CH:7]=1.[CH:33]1([C:36]#[CH:37])[CH2:35][CH2:34]1.C(NC(C)C)(C)C.[NH4+].[OH-]>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.C(OCC)(=O)C.CN(C=O)C>[CH:33]1([C:36]#[C:37][C:2]2[CH:3]=[CH:4][C:5]3[C:18]4[N:17]=[C:16]([C:19]5[C:26]([C:27]#[N:28])=[CH:25][CH:24]=[CH:23][C:20]=5[C:21]#[N:22])[NH:15][C:14]=4[C:13]4[C:8](=[CH:9][C:10]([C:29]([OH:32])([CH3:31])[CH3:30])=[CH:11][CH:12]=4)[C:6]=3[CH:7]=2)[CH2:35][CH2:34]1

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 14923Ammonium HydroxideHCID 138823CyclopropylacetyleneHCID 16731188HCID 16731188, compound

Product 1

HCID 178458164HCID 178458164, compoundYield 28.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
62.5 °C

Procedure

A round bottomed flask containing 2-[6-bromo-9-(1-hydroxy-1-methylethyl)-1H-phenanthro[9,10-d]imidazol-2-yl]isophthalonitrile from Example 87 (1.26 g, 2.62 mmol), Pd(PPh3)4 (190 mg, 0.27 mmol) and copper iodide (100 mg, 0.52 mmol) was purged with nitrogen for 15 minutes, followed by addition of DMF (50 mL), cyclopropyl acetylene (1.4 mL, 21 mmol) and di-isopropylamine (560 μL, 4 mmol). The resulting mixture was heated at 60-65° C. for 3.5 h, cooled to room temperature and then poured into a mixture of NH4OH and ethyl acetate and stirred for 1 h. The aqueous phase was extracted with ethyl acetate, the organic layer washed once with water, once with brine, dried over Na2SO4, filtered and concentrated. The material obtained after purification by flash chromatography on silica (30-100% ethyl acetate in toluene) was swished in toluene for 2 h and then filtered to afford 2-[6-(cyclopropylethynyl)-9-(1-hydroxy-1-methylethyl)-1H-phenanthro[9,10-d]imidazol-2-yl]isophthalonitrile as a yellow solid (350 mg). The mother liquor was combined with the mixed fractions and re-purified by flash chromatography on silica (3-40% acetonitrile in toluene) to afford 286 mg the bis-nitrile (total yield 52%).

Workup

  1. customwas purged with nitrogen for 15 minutes
  2. temperaturecooled to room temperature
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe organic layer washed once with water, once with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material obtained
  9. customafter purification by flash chromatography on silica (30-100% ethyl acetate in toluene)
  10. waitwas swished in toluene for 2 h
  11. filtrationfiltered

Sources & evidence

ORD record
ord-905668848a3548e999617a6de2cbf99f
Source dataset
uspto-grants-2011_05
Patent number
US07943649B2

Reaction notes

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