Potassium Carbonate → 3-fluoro-4-[2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy]-phenyl-carbamic acid t-butyl ester

HRID 1851093Notes

Reaction equation

HRID 1851093 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:10][C:3]=12.[C:25]([O:29][C:30](=[O:40])[NH:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[C:34]([F:39])[CH:33]=1)([CH3:28])([CH3:27])[CH3:26].C1(C2C=CC=CC=2C2C(C(C)C)=C(C3CCCCC3)C(C(C)C)=C(P)C=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:25]([O:29][C:30](=[O:40])[NH:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:9]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[CH:10][C:3]=23)=[C:34]([F:39])[CH:33]=1)([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11708410tert-Butyl (3-Fluoro-4-hydroxyphenyl)carbamateHCID 583683444-chloro-2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridineHCID 87317025Dicyclohexyl-phosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 583683903-fluoro-4-[2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yloxy]-phenyl-carbamic acid t-butyl esterYield 84%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

4-Chloro-2-phenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (312 mg, 0.87 mmol) and (3-fluoro-4-hydroxy-phenyl)-carbamic acid t-butyl ester (336 mg, 1.48 mmol) were dissolved in anhydrous toluene (5 mL) under nitrogen atmosphere. After adding dicyclohexyl-phosphino-2,4,6-triisopropylbiphenyl (41 mg, 0.087 mmol), Pd2 dba3 (40 mg, 0.044 mmol) and potassium carbonate, the mixture was heated at 110° C. The resulting reaction mixture was cooled to room temperature and filtered by passing through a celite pad. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane: ethyl acetate=9:1) to give the target compound as a white solid (404 mg, 0.73 mmol, 84% yield).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas cooled to room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (hexane: ethyl acetate=9:1)

Sources & evidence

ORD record
ord-31bfbbe594f647fd980865b2eeb8dafe
Source dataset
uspto-grants-2015_02
Patent number
US08957102B2

Reaction notes

Loading…