Trimethylsilylacetylene → 6-((Trimethylsilyl)ethynyl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888601Notes

Reaction equation

HRID 1888601 reaction equation
Br[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:37][Si:38]([C:41]#[CH:42])([CH3:40])[CH3:39]>O1CCOCC1.C(Cl)Cl.CO.[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>[CH3:37][Si:38]([C:41]#[C:42][C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1)([CH3:40])[CH3:39]

Participants

9

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 582663876-Bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 582666556-((Trimethylsilyl)ethynyl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-bromo-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (170 mg, 0.40 mmol), copper(I) iodide (7.7 mg, 0.04 mmol), and N,N-diisopropylethylamine (0.21 mL, 1.2 mmol) in anhydrous 1,4-dioxane (3 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (47 mg, 0.04 mmol) and (trimethylsilyl)acetylene (0.34 mL, 2.4 mmol) were added and the reaction mixture heated at 110° C. for 1 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in methanol) to afford a brown residue that was taken to the next step without further purification.

Workup

  1. customwas degassed
  2. customflushed with nitrogen
  3. customThe cooled reaction mixture
  4. washwashed with water (15 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in methanol)
  11. customto afford a brown residue that
  12. customwas taken to the next step without further purification

Sources & evidence

ORD record
ord-49434804a2a54cc58e33fc6f66e4a484
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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