HCID 57537453, compound → HCID 67280240, compound

HRID 1693704Notes

Reaction equation

HRID 1693704 reaction equation
[Cl:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][N:5]=[C:4]2[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:19][C:3]=12.Br[C:29]1[CH:30]=[C:31]([CH:35]([OH:41])[C:36]([N:38]([CH3:40])[CH3:39])=[O:37])[CH:32]=[N:33][CH:34]=1>C1COCC1.C(#N)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:1][C:2]1[C:7]([C:29]2[CH:30]=[C:31]([CH:35]([OH:41])[C:36]([N:38]([CH3:39])[CH3:40])=[O:37])[CH:32]=[N:33][CH:34]=2)=[CH:6][N:5]=[C:4]2[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:26])[CH3:27])[CH:18]=[CH:19][C:3]=12

Participants

5

Reactant 2

HCID 57537453HCID 57537453, compoundHCID 57537619HCID 57537619, compound

Product 1

HCID 67280240HCID 67280240, compoundYield 85.4%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (1.3 g, 3.3 mmol), 2-(5-bromo-pyridin-3-yl)-2-hydroxy-N,N-dimethyl-acetamide (0.8 g, 3.3 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (133 mg, 0.2 mmol) in THF/Acetonitrile/saturated NaHCO3 (20 ml/20 ml/20 ml) was stirred at 70° C. overnight. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (2×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 2-{5-[4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]pyridine-3-yl}-2-hydroxy-N,N-dimethyl-acetamide (1.3 g, 85% yield). 1H NMR (500 MHz, DMSO-d6) δ 0.05 (s, 9H), 0.92 (t, 2H), 2.95 (d, 6H), 3.62 (t, 2H), 5.68 (s, 1H), 6.77 (s, 1H), 7.96, (s, 1H), 7.98 (s, 1H), 8.41 (s, 1H), 8.71 (s, 1H), 8.72 (s, 1H). MS: m/z 461.3 (M+H+).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with ethyl acetate (2×)
  3. extractionThe combined organic layers were extracted with brine
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-6b27de46c4054876ba3dbdbe661d900a
Source dataset
uspto-grants-2012_04
Patent number
US08158647B2

Reaction notes

Loading…