Potassium Phosphate, Tribasic → [3-(1-methyl-1H-indol-2-yl)-pyridin-4-yl]-methanol

HRID 593585Notes

Reaction equation

HRID 593585 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1B(O)O.Br[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH2:21][OH:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH2:21][OH:22]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 22733820(1-Methyl-1H-indol-2-yl)boronic acidHCID 46840038(3-Bromopyridin-4-yl)methanol

Product 1

HCID 58215608[3-(1-methyl-1H-indol-2-yl)-pyridin-4-yl]-methanol

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A microwave reactor is charged with 1-methyl-indole-2-boronic acid (1.18 g, 6.78 mmol), (3-bromo-pyridin-4-yl)-methanol (0.850 g, 4.52 mmol), potassium phosphate (1.91 g, 9.04 mmol) and DMF (10 mL). The reactor is evacuated and filled with nitrogen thrice and Pd(PPh3)4 (0.261 g, 0.226 mmol) is added. The reactor is evacuated and filled with nitrogen thrice again. The mixture is heated to 120° C. for 1 h under microwave irradiation, then diluted with ethyl acetate and washed with water thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo to give a residue which is purified by silica gel flash chromatography (dichloromethane-methanol, 19:1) to afford [3-(1-methyl-1H-indol-2-yl)-pyridin-4-yl]-methanol as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 3.58 (s, 3H), 4.57 (s, 2H), 6.54 (s, 1H), 7.14 (t, J=7.5 Hz, 1H), 7.27 (ddd, J=7.6, 1.1 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.81 (d, J=5.1 Hz, 1H), 8.49 (s, 1H), 8.67 (d, J=5.1 Hz, 1H). HRMS (ESI) m/z 239.1177 [(M+H)+ Calcd for C15H15N2O: 239.1184].

Workup

  1. customThe reactor is evacuated
  2. additionis added
  3. customThe reactor is evacuated
  4. additionfilled with nitrogen thrice again
  5. additiondiluted with ethyl acetate
  6. washwashed with water thrice
  7. dry with materialThe organic layer is dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a residue which
  10. customis purified by silica gel flash chromatography (dichloromethane-methanol, 19:1)

Sources & evidence

ORD record
ord-3adc5576294f4ebbab3294db1cea2b0b
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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