Tetrahydrofuran → 2-cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1521958Notes

Reaction equation

HRID 1521958 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][C:9]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)=[CH:10][C:3]=12.[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:27][CH3:28])=[C:22](B(O)O)[CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCCC1>O.C(OCC)(=O)C>[CH:11]1([C:9]2[NH:8][C:4]3=[N:5][CH:6]=[CH:7][C:2]([C:20]4[CH:19]=[C:18]([F:17])[CH:23]=[CH:22][C:21]=4[O:27][CH3:28])=[C:3]3[CH:10]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 904126714-Chloro-2-cyclohexyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 904115382-cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of Example 98B (200 mg, 0.852 mmol), (5-fluoro-2-methoxyphenyl)boronic acid (188 mg, 1.108 mmol), phenylallylchloro[1,3-bis(diisopropylphenyl)-2-imidazol-2-ylidene]palladium(II) (50 mg, 0.077 mmol) and potassium phosphate (543 mg, 2.56 mmol) in 8 mL 3:1 tetrahydrofuran:water was purged with nitrogen and heated under nitrogen at 60° C. for 4 hours. The cooled mixture was diluted with water and ethyl acetate and filtered through diatomaceous earth. The mixture was extracted into ethyl acetate (twice) and the combined extracts were rinsed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (1:1 ethyl acetate:hexanes) provided only a small amount of material. The column was washed with 10% methanol/dichloromethane and the remainder of the material eluted. The combined residue was suspended in diethyl ether and the solids were collected and rinsed with diethyl ether to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ 1.20-1.48 (m, 5H) 1.64-1.76 (m, 3H) 1.99-2.02 (m, 2H) 2.70-2.73 (m, 1H) 3.72 (s, 3H) 5.92 (s, 1H) 6.99 (d, J=5.08 Hz, 1H) 7.15-7.27 (m, 3H) 8.12 (d, J=4.75 Hz, 1H) 11.50 (s, 1H). MS (DCI) m/e 325 (M+H)+.

Workup

  1. filtrationfiltered through diatomaceous earth
  2. extractionThe mixture was extracted into ethyl acetate (twice) and the combined extracts
  3. washwere rinsed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (1:1 ethyl acetate:hexanes)
  8. customprovided only a small amount of material
  9. washThe column was washed with 10% methanol/dichloromethane
  10. washthe remainder of the material eluted
  11. customthe solids were collected
  12. washrinsed with diethyl ether

Sources & evidence

ORD record
ord-9af9e3520e1541efacebd5fce5990a38
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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