Hydrochloric Acid → 2-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-propionic acid

HRID 886597Notes

Reaction equation

HRID 886597 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1.Br[C:36]1[CH:37]=[C:38]([CH:42]([CH3:46])[C:43]([OH:45])=[O:44])[CH:39]=[CH:40][CH:41]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C(#N)C.C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:40]3[CH:39]=[C:38]([CH:42]([CH3:46])[C:43]([OH:45])=[O:44])[CH:37]=[CH:36][CH:41]=3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 127979542-(3-Bromophenyl)propanoic acidHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 598250722-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-propionic acid

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (0.84 g, 1.7 mmol) and 2-(3-Bromo-phenyl)-propionic acid (0.39 g, 1.7 mmol) in a 20 mL microwave reaction flask was added THF (6 mL), acetonitrile (6 mL), and sodium carbonate (1 N in water, 6 mL, 6 mmol). The resulting suspension was purged with nitrogen for 1 minute. Dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (62 mg, 76 mmol) was added and the purging was continued for another minute. The flask was sealed and was irradiated in a microwave reactor to 90° C. for 10 minutes. The reaction mixture was adjusted to pH 4 using 1 N hydrochloric acid, extracted with ethyl acetate (10 mL×3). The combine organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane to afford 2-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-propionic acid as a off white solid (497 mg, 58%). MS: m/z 504 (M+H+).

Workup

  1. customin a 20 mL microwave reaction flask
  2. customThe resulting suspension was purged with nitrogen for 1 minute
  3. customThe flask was sealed
  4. customwas irradiated in a microwave reactor to 90° C. for 10 minutes
  5. extractionextracted with ethyl acetate (10 mL×3)
  6. dry with materialThe combine organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane

Sources & evidence

ORD record
ord-a0f64c5731ef46efb5125c6f54fa3d6a
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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