2-Methyl-3-butyn-2-ol → HCID 86693487, compound

HRID 575430Notes

Reaction equation

HRID 575430 reaction equation
Br[C:2]1[C:3]([F:20])=[CH:4][C:5]2[CH:17]3[CH2:18][CH:15]([CH2:16]3)[C:8]3[NH:9][C:10]([C:12]([NH2:14])=[O:13])=[N:11][C:7]=3[C:6]=2[CH:19]=1.CN(C)C=O.C(N(CC)CC)C.[CH3:33][C:34]([OH:38])([C:36]#[CH:37])[CH3:35]>C(#N)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:20][C:3]1[C:2]([C:37]#[C:36][C:34]([OH:38])([CH3:35])[CH3:33])=[CH:19][C:6]2[C:7]3[N:11]=[C:10]([C:12]([NH2:14])=[O:13])[NH:9][C:8]=3[CH:15]3[CH2:16][CH:17]([C:5]=2[CH:4]=1)[CH2:18]3

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 22056947triethylamine N,N-dimethylformamideHCID 86693485HCID 86693485, compound

Product 1

HCID 86693487HCID 86693487, compoundYield 27.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Into a pressure tube containing a solution 9-bromo-8-fluoro-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide (47 mg, 0.14 mmol) in 1:1 N,N-dimethylformamide/triethylamine (0.8 mL) was introduced 2-methyl-3-butyn-2-ol (235 mg, 2.80 mmol), copper(I) iodide (2 mg, 0.01) and nitrogen gas bubbled through the solution for 3 minutes. Bis(triphenylphosphine)palladium(II) chloride (10 mg, 0.01 mmol) was added and nitrogen bubbling continued a further two minutes before the pressure tube was closed under nitrogen. The reaction mixture was warmed to 80° C. for 8 hr. After cooling to room temperature, the reaction mixture was evaporated in vacuo and the residue re-dissolved in ethyl acetate (15 mL). This solution was washed with water (2×5 mL) and brine (5 mL). The organic extract was dried over sodium sulfate, filtered and the filtrate absorbed onto silica gel. Purification by silica gel flash column chromatography (eluent: dichloromethane containing a 0-8% gradient of methanol) furnished partially purified product as a brown oil. After several acetonitile solubilisation-evaporation (in vacuo) cycles, a grey-brown solid was obtained which was slurried in acetonitrile (0.4 mL) and collected by filtration to furnish the title compound (13 mg, 0.038 mmol, 27%) as a grey solid: 1H NMR (500 MHz, d4-methanol) δ 1.59 (s, 6H), 1.63 (d, J=11.03 Hz, 2H), 2.85-2.95 (m, 2H), 3.44 (td, J=6.94, 3.78 Hz, 1H), 3.63 (td, J=8.04, 3.78 Hz, 1H), 6.86 (d, J=10.40 Hz, 1H), 8.25 (d, J=7.57 Hz, 1H); M+1=340.

Workup

  1. custombubbled through the solution for 3 minutes
  2. customwas closed under nitrogen
  3. temperatureAfter cooling to room temperature
  4. customthe reaction mixture was evaporated in vacuo
  5. dissolutionthe residue re-dissolved in ethyl acetate (15 mL)
  6. washThis solution was washed with water (2×5 mL) and brine (5 mL)
  7. extractionThe organic extract
  8. dry with materialwas dried over sodium sulfate
  9. filtrationfiltered
  10. customthe filtrate absorbed onto silica gel
  11. customPurification by silica gel flash column chromatography (eluent
  12. customdichloromethane containing a 0-8% gradient of methanol) furnished partially purified product as a brown oil
  13. customAfter several acetonitile solubilisation-evaporation (in vacuo) cycles
  14. customa grey-brown solid was obtained which
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-b8a0edca79784f9b9804ecfec3b4b73f
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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