1-Chloro-4-(chloromethyl)benzene → HCID 53496815, compound

HRID 45577Notes

Reaction equation

HRID 45577 reaction equation
C[Si](C#C)(C)C.C([N:9]([CH2:12][CH3:13])[CH2:10][CH3:11])C.I[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[CH:21][CH:22]=2)[N:17]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:16]=1.[Cl:31][C:32]1[CH:37]=[CH:36]C(CCl)=[CH:34][CH:33]=1.[N-:40]=[N+:41]=[N-].[Cs+]>C1COCC1.CO.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.[Cu]I>[Cl:31][C:32]1[CH:37]=[CH:36][C:13]([CH2:12][N:9]2[CH:10]=[C:11]([C:15]3[C:23]4[C:18](=[N:19][CH:20]=[CH:21][CH:22]=4)[N:17]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:16]=3)[N:41]=[N:40]2)=[CH:34][CH:33]=1

Participants

10

Reactant 5

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 89817Cesium azideHCID 23529164tert-Butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Product 1

HCID 53496815HCID 53496815, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2.1 0.43 ml (3.00 mmol) of trimethylsilylacetylene and 0.55 ml (4.00 mmol) of triethylamine are added successively to a suspension, kept under argon, of 28 mg (0.04 mmol) of bis(triphenylphosphine)palladium dichloride, 16 mg (0.08 mmol) of copper(I) iodide and 688 mg (2.00 mmol) of tert-butyl 3-iodo-(1H)-pyrrolo[2,3-b]pyridine-1-carboxylate in 10 ml of THF, and the mixture is stirred at room temperature for one hour under argon. Then, for the removal of excess trimethylsilylacetylene, argon is passed through the reaction mixture for 5 minutes. 2.00 ml (2.0 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF are subsequently added, and the reaction mixture is stirred at room temperature for 30 minutes. A solution of 322 mg (2.00 mmol) of 1-chloro-4-(chloromethyl)benzene in 5 ml of methanol, 350 mg (2.00 mmol) of caesium azide and 5 ml of methanol is then added, and the reaction mixture is stirred at room temperature for 51 hours. The reaction mixture is adsorbed onto kieselguhr and chromatographed on a silica-gel column with petroleum ether/ethyl acetate 2:1, giving tert-butyl 3-[1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl]pyrrolo[2,3-b]pyridine-1-carboxylate as pale-yellow solid; ESI 410.

Workup

  1. customThen, for the removal of excess trimethylsilylacetylene, argon
  2. waitis passed through the reaction mixture for 5 minutes
  3. addition2.00 ml (2.0 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF are subsequently added
  4. stirringthe reaction mixture is stirred at room temperature for 30 minutes
  5. stirringthe reaction mixture is stirred at room temperature for 51 hours
  6. customchromatographed on a silica-gel column with petroleum ether/ethyl acetate 2:1

Sources & evidence

ORD record
ord-5de5cbf1f9f44304a338bdc2fcb69485
Source dataset
uspto-grants-2013_09
Patent number
US08541584B2

Reaction notes

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