Water → 2-(5-bromopyridin-3-yl)-1H-indole

HRID 1630859Notes

Reaction equation

HRID 1630859 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.[Br:20][C:21]1[CH:22]=[N:23][CH:24]=[C:25](I)[CH:26]=1.C([O-])([O-])=O.[K+].[K+].O>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>[Br:20][C:21]1[CH:26]=[C:25]([C:9]2[NH:8][C:16]3[C:11]([CH:10]=2)=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:24]=[N:23][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 8204093-Bromo-5-iodopyridine2×HCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 582156752-(5-bromopyridin-3-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

A flask containing 1-(tert-butoxycarbonyl)-1H-indol-2-ylboronic acid (2 g, 7.66 mmol), 3-bromo-5-iodopyridine (1.45 g, 5.11 mmol), 2M K2CO3 in water (5.11 mL, 10.21 mmol), PS—Pd(PPh3)4 (2.84 g, 0.255 mmol) is flushed with N2 and dioxane (50 mL) is added. The mixture is stirred at 60° C. for 3 h, whereupon another portion of 3-bromo-5-iodopyridine (300 mg, 1.06 mmol) is added. The mixture is stirred at 60° C. overnight. The mixture is cooled to room temperature and silica gel (20 g) is added. The suspension is concentrated in vacuo and the residue is placed under high vacuum at 60° C. over the weekend. The mixture is purified by silica chromatography eluting with a 1:9 to 7:3 EtOAc-heptane gradient to give 2-(5-bromopyridin-3-yl)-1H-indole. MS (ESI) m/z 273.0, 275.1 (M+H)+.

Workup

  1. customis flushed with N2 and dioxane (50 mL)
  2. additionis added
  3. additionis added
  4. temperatureThe mixture is cooled to room temperature
  5. additionsilica gel (20 g) is added
  6. concentrationThe suspension is concentrated in vacuo
  7. customis placed under high vacuum at 60° C. over the weekend
  8. customThe mixture is purified by silica chromatography
  9. washeluting with a 1:9 to 7:3 EtOAc-heptane gradient

Sources & evidence

ORD record
ord-42207d135c2940658a5d3e1d7ede12c4
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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