Diisopropylamine → 2-[5-(5-Bromo-pyridin-2-ylethynyl)-indol-1-yl]-ethanol

HRID 1916709Notes

Reaction equation

HRID 1916709 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][CH2:21][OH:22])[CH:15]=[CH:14]2)#[CH:10].C(NC(C)C)(C)C>C1COCC1.[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>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:10]#[C:9][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH2:21][OH:22])[CH:15]=[CH:14]3)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 693532,5-Dibromopyridine2×HCID 859695012-(5-Ethynyl-indol-1-yl)-ethanol

Product 1

HCID 673628532-[5-(5-Bromo-pyridin-2-ylethynyl)-indol-1-yl]-ethanol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Under an N2 atmosphere 29.4 g (124 mmol) 2,5-dibromo-pyridine, 241 mg (1.3 mmol) CuI and 888 mg (1.3 mmol) Pd(PPh3)2Cl2 are added to a solution of 23.0 g (124 mmol) 2-(5-ethynyl-indol-1-yl)-ethanol and 35 mL (248 mmol) diisopropylamine in 1150 mL THF and the reaction mixture is heated to 50° C. for 3.5 h. Another 241 mg CuI and 888 mg Pd(PPh3)2Cl2 and 9 g (38 mmol) 2,5-dibromo-pyridine are added, the mixture is stirred for a further 2.5 h at 50° C., 64 h at RT and a further 8 h at 60° C. The mixture is evaporated down i. vac., the residue is combined with 500 mL 3% NH3 solution and 800 mL EtOAc. The precipitate formed is filtered off, washed with water and dried at 50° C. The two phases of the filtrate are separated and the organic phase is evaporated down i.vac. The residue is stirred vigorously with 500 mL PE/diisopropylether (1:1) and suction filtered. The two product fractions are then combined.

Workup

  1. customThe mixture is evaporated down i
  2. customThe precipitate formed
  3. filtrationis filtered off
  4. washwashed with water
  5. customdried at 50° C
  6. customThe two phases of the filtrate are separated
  7. customthe organic phase is evaporated down i.vac
  8. stirringThe residue is stirred vigorously with 500 mL PE/diisopropylether (1:1) and suction
  9. filtrationfiltered

Sources & evidence

ORD record
ord-b885adefb454455f8329155c07bcafc3
Source dataset
uspto-grants-2013_12
Patent number
US08618132B2

Reaction notes

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