Ethyl Acetate → 5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-nicotinic acid ethyl ester

HRID 1865594Notes

Reaction equation

HRID 1865594 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][CH:9]=[C:10](B(O)O)[CH:11]=1)=[O:5])[CH3:2].Br[C:16]1[CH:17]=[C:18]2[C:24](I)=[N:23][N:22]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:19]2=[N:20][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:40]([O:43][CH2:44][CH3:45])(=O)C>O>[CH2:1]([O:3][C:4](=[O:5])[C:6]1[CH:11]=[C:10]([C:16]2[CH:17]=[C:18]3[C:24]([C:10]4[CH:11]=[CH:6][CH:4]=[CH:45][C:44]=4[O:43][CH3:40])=[N:23][N:22]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:19]3=[N:20][CH:21]=2)[CH:9]=[N:8][CH:7]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 55265795(5-(Ethoxycarbonyl)pyridin-3-yl)boronic acidHCID 598361345-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 598360525-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-nicotinic acid ethyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3-ethoxycarbonyl-5-pyridinylboronic acid (529 mg, 1.91 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichlormethane adduct (66 mg, 0.09 mmol) and 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (780 mg, 1.80 mmol) acetonitrile (5 mL) and 2 M aqueous solution of sodium carbonate (5 mL) were added and the mixture was irradiated in a Personal Chemistry Optimizer to 90° C. for 30 minutes. The crude reaction mixture was distributed between ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-nicotinic acid ethyl ester (552 mg, 61% yield) as a yellow oil. 1H-NMR (500 MHz, d6-DMSO) δ 9.24 (d, 1H), 9.12 (d, 1H), 9.03 (d, 1H), 8.60 (t, 1H), 8.56 (d, 1H), 7.66 (dd, 1H), 7.51 (ddd, 1H), 7.25 (dd, 1H), 7.12 (dt, 1H), 5.88 (s, 2H), 4.40 (q, 2H), 3.87 (s, 3H), 3.71 (t, 2H), 1.37 (t, 3H), 0.87 (t, 2H), −0.073 (t, 9H). MS: m/z 505 [MH+].

Workup

  1. additionwere added
  2. customthe mixture was irradiated in a Personal Chemistry Optimizer to 90° C. for 30 minutes
  3. customThe crude reaction mixture
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-42afc89b78dc4bb4b0397b95f6d5ff41
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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