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

HRID 1865666Notes

Reaction equation

HRID 1865666 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]([CH2:42][C:43]([OH:45])=[O:44])[CH:39]=[CH:40][CH:41]=1.C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[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:36]3[CH:37]=[C:38]([CH2:42][C:43]([OH:45])=[O:44])[CH:39]=[CH:40][CH:41]=3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])[N:10]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 74653(3-Bromophenyl)acetic 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 57975859{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acidYield 67%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 (500 mg, 1.04 mmol) and 3-bromophenylacetic acid (268 mg, 1.25 mmol) in a 20 mL microwave reaction flask was added THF (3 mL), acetonitrile (3 mL) and sodium carbonate (3 mL, 1 N aqueous solution, 3 mmol). The mixture was bubbled with N2 for 1 min. dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) (73 mg, 10% mol) was added and the bubbling continued for another minute. The flask was sealed and irradiated with microwave in Emrys Optimizer at 120° C. for 20 min. The reaction mixture was partitioned between aqueous saturated sodium chloride and ethyl acetate (15 mL: 15 mL). The aqueous layer was extracted with ethyl acetate (10 mL×2). Normal work up of the combined organic layers and purification with flash chromatography on silsca gel using a gradient of methanol in dichloromethane yielded {3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid as a yellow solid (340 mg, 67% yield). MS: m/z 490 (M+H+).

Workup

  1. customin a 20 mL microwave reaction flask
  2. customThe mixture was bubbled with N2 for 1 min. dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) (73 mg, 10% mol)
  3. additionwas added
  4. customThe flask was sealed
  5. customirradiated with microwave in Emrys Optimizer at 120° C. for 20 min
  6. customThe reaction mixture was partitioned between aqueous saturated sodium chloride and ethyl acetate (15 mL: 15 mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×2)
  8. customNormal work up of the combined organic layers and purification with flash chromatography on silsca gel

Sources & evidence

ORD record
ord-791c1a1b459f41aba842172c92d77a35
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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