(Pyridin-4-yl)boronic acid → 5-(2-(4-(ethylsulfonyl)piperazin-1-yl)-5-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

HRID 538437Notes

Reaction equation

HRID 538437 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:11]1[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:14]([N:24]2[CH2:29][CH2:28][N:27]([S:30]([CH2:33][CH3:34])(=[O:32])=[O:31])[CH2:26][CH2:25]2)=[N:13][C:12]=1[C:35]1[CH:36]=[C:37]([O:42][CH3:43])[C:38]([NH2:41])=[N:39][CH:40]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].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>[CH2:33]([S:30]([N:27]1[CH2:28][CH2:29][N:24]([C:14]2[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:11]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[C:12]([C:35]3[CH:36]=[C:37]([O:42][CH3:43])[C:38]([NH2:41])=[N:39][CH:40]=3)[N:13]=2)[CH2:25][CH2:26]1)(=[O:32])=[O:31])[CH3:34]

Participants

6

Reactant 2

HCID 2734379(Pyridin-4-yl)boronic acidHCID 665911635-(5-bromo-2-(4-(ethylsulfonyl)piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

Product 1

HCID 665912915-(2-(4-(ethylsulfonyl)piperazin-1-yl)-5-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of pyridin-4-ylboronic acid (17.0 mg, 0.14 mmol) and 5-(5-bromo-2-(4-(ethylsulfonyl)piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine (26.5 mg, 0.05 mmol) in DME (1.5 mL) and 2.0 M aqueous Na2CO3 (0.5 mL) was sparged with Ar for 2 min. Tetrakis(triphenylphosphine)palladium(0) (10.6 mg, 9.2 μmol) was added. The mixture was sparged with Ar for an additional 2 min and was irradiated in a sealed tube in a microwave reactor at 115° C. for 15 min. The reaction mixture was extracted with EtOAc (3×10 mL). The combined organic layers were washed with sat aqueous NaHCO3 (30 mL), brine (30 mL), dried over Na2SO4, filtered and concentrated in vacuo. The material purified by preparative TLC (SiO2, 0.25 mm, 95:5 DCM-MeOH) to afford 5-(2-(4-(ethylsulfonyl)piperazin-1-yl)-5-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine was isolated as colorless solid: LCMS (m/z): 574.3 (MH+), tR=0.68 min.

Workup

  1. customwas sparged with Ar for 2 min
  2. customThe mixture was sparged with Ar for an additional 2 min
  3. customwas irradiated in a sealed tube in a microwave reactor at 115° C. for 15 min
  4. extractionThe reaction mixture was extracted with EtOAc (3×10 mL)
  5. washThe combined organic layers were washed with sat aqueous NaHCO3 (30 mL), brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe material purified by preparative TLC (SiO2, 0.25 mm, 95:5 DCM-MeOH)

Sources & evidence

ORD record
ord-dd2c9dff34cb4386b29f804997bc033c
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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