2-Methyl-3-butyn-2-ol → HCID 58266403, compound

HRID 1505955Notes

Reaction equation

HRID 1505955 reaction equation
Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH3:25][C:26]([OH:30])([C:28]#[CH:29])[CH3:27]>O1CCOCC1.C(Cl)Cl.O.[Cu]I.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>[OH:30][C:26]([CH3:27])([CH3:25])[C:28]#[C:29][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1

Participants

8

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 58266568HCID 58266568, compound

Product 1

HCID 58266403HCID 58266403, compoundYield 124.2%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

In a flame dried flask, a mixture of 3-bromo-9-(2-trimethylsilanylethoxymethyl)-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (203 mg, 0.503 mmol) and copper (I) iodide (9.58 mg, 50.3 μmol) in 1,4-dioxane (5.3 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (58.1 mg, 50.3 μmol) and 2-methyl-3-butyn-2-ol (244 μL, 2.52 mmol) were added and the reaction mixture was degassed, purged with nitrogen, and heated at 105° C. for 70 min. The cooled reaction mixture was diluted with DCM and water, the layers separated, and the aqueous phase extracted into DCM. The combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in EtOAc and absorbed onto silica gel for purification by flash chromatography (silica, 25 g column, Biotage, 1-100% EtOAc in heptane) to afford further title compound as a white-yellow solid (254 mg, 124%). The solid was used without further purification. 1H NMR (DMSO-D6, 400 MHz,): 9.33 (s, 1H), 8.98 (s, 1H), 8.91 (d, J=1.9 Hz, 1H), 8.76 (d, J=1.9 Hz, 1H), 6.03 (s, 2H), 5.55 (s, 1H), 3.57 (t, J=7.9 Hz, 2H), 1.51 (s, 6H), 0.82 (t, J=8.0 Hz, 2H), −0.16 (s, 9H).

Workup

  1. customIn a flame dried flask
  2. customwas degassed
  3. customflushed with nitrogen
  4. customthe reaction mixture was degassed
  5. custompurged with nitrogen
  6. customThe cooled reaction mixture
  7. customthe layers separated
  8. extractionthe aqueous phase extracted into DCM
  9. dry with materialThe combined organic phase was dried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. dissolutionThe resultant residue was dissolved in EtOAc
  12. customabsorbed onto silica gel for purification by flash chromatography (silica, 25 g column, Biotage, 1-100% EtOAc in heptane)

Sources & evidence

ORD record
ord-3906bfa56cc74fa5a9c8babf21f452c1
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

Loading…