Potassium Phosphate, Tribasic → 3-[bis[[(1,1-dimethylethyl)oxy]carbonyl]amino]-5-(6-chloro-1-methyl-1H-indol-2-yl)-pyridine

HRID 593660Notes

Reaction equation

HRID 593660 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]1[CH:10]=[N:11][CH:12]=[C:13](Br)[CH:14]=1)=[O:7])([CH3:4])[CH3:3].[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=2)[CH:26]=[C:25]1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.CN(C=O)C>[CH3:1][C:2]([O:5][C:6]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:25]2[N:24]([CH3:23])[C:32]3[C:27]([CH:26]=2)=[CH:28][CH:29]=[C:30]([Cl:33])[CH:31]=3)[CH:14]=1)=[O:7])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 441195946-Chloro-1-methyl-1H-indole-2-boronic acidHCID 582155715-bromo-3-(N,N-bis-boc-amino)pyridine

Product 1

HCID 582155493-[bis[[(1,1-dimethylethyl)oxy]carbonyl]amino]-5-(6-chloro-1-methyl-1H-indol-2-yl)-pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A flask is charged with 3-[bis[[(1,1-dimethylethyl)oxy]carbonyl]amino]-5-bromo-pyridine (1.12 g, 3.0 mmol), N-methyl-6-chloroindole-2-boronic acid (754 mg, 3.6 mmol), finely crushed potassium phosphate (1.27 g, 6.0 mmol) and DMF (20 mL). After degassing for 15 min, Pd(PPh3)4 (173 mg, 0.15 mmol) is added. The flask is flushed with nitrogen and the mixture is heated to 90° C. and stirred for 5 h. The mixture is then cooled to room temperature and poured into water (100 mL). The mixture is extracted with EtOAc three times and the combined organic phase is washed with water (10 mL) twice. The organic phase is then dried over Na2SO4 and concentrated. The residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:9) to give 3-[bis[[(1,1-dimethylethyl)oxy]carbonyl]amino]-5-(6-chloro-1-methyl-1H-indol-2-yl)-pyridine. MS (ESI) m/z 458.1 (M+H)+.

Workup

  1. customAfter degassing for 15 min
  2. customThe flask is flushed with nitrogen
  3. temperatureThe mixture is then cooled to room temperature
  4. additionpoured into water (100 mL)
  5. extractionThe mixture is extracted with EtOAc three times
  6. washthe combined organic phase is washed with water (10 mL) twice
  7. dry with materialThe organic phase is then dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:9)

Sources & evidence

ORD record
ord-01d7e9381d184c99966387b4aa131ce6
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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