Cyclohexanone → HCID 59699887, compound

HRID 729832Notes

Reaction equation

HRID 729832 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:11]1(=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.O[C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>CO.O.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[C:19]1([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:13]4[CH:12]=[C:11]([OH:17])[CH:16]=[CH:15][CH:14]=4)[CH:3]=3)[NH:8][CH:9]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=1

Participants

9

Reactant 4

HCID 7967CyclohexanoneHCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 59699887HCID 59699887, compoundYield 12%

Reagents, catalysts & solvents 4

HCID 178418903HCID 178418903, compoundCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.507 mmol) in MeOH (1 mL) was added cyclohexanone (52 uL, 1.015 mmol). The reaction mixture was stirred at 80° C. for 16 h then concentrated in vacuo. To the residue was added 3-hydroxyphenyl boronic acid (91 mg, 0.66 mmol), dichlorobis (triphenylphosphino)palladium (II) (18 mg, 0.025 mmol), and 2 mL of a 1:1 mixture of acetonitrile, and a 2 M solution of sodium carbonate in water. The reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 600 s. The reaction mixture was diluted with methanol, filtered, and the filtrate was adsorbed on silica gel. Purification on silica gel with a gradient of MeOH/CH2Cl2 afforded 3-(3-cyclohex-1-enyl-1H-pyrrolo[2,3-b]pyridine-5-yl)-phenol as an off-white solid (12.6 mg, 12% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.64 (m, 2H), 1.74 (m, 2H), 2.23 (m, 2H), 2.42 (m, 2H), 6.27 (m, 1H), 6.74 (dd, J=2.0, 8.0 Hz, 1H), 7.05 (s, 1H), 7.11 (d, J=7.5 Hz, 1H), 7.26 (t, J=8.0 Hz, 1H), 7.50 (d, J=2.0 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.42 (d, J=2.0 Hz, 1H), 9.51 (broad s, 1H), 11.7 (s, 1H). MS: m/z 291 (M+H+).

Workup

  1. concentrationthen concentrated in vacuo
  2. additionTo the residue was added
  3. waitThe reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 600 s
  4. filtrationfiltered
  5. customPurification on silica gel with a gradient of MeOH/CH2Cl2

Sources & evidence

ORD record
ord-afc09778cc5b49738061449d456b27fd
Source dataset
uspto-grants-2009_09
Patent number
US07582637B2

Reaction notes

Loading…