Citric Acid → 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acid

HRID 1865622Notes

Reaction equation

HRID 1865622 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.[NH2:35][C:36]1[C:44]([CH3:45])=[CH:43][C:42](I)=[CH:41][C:37]=1[C:38]([OH:40])=[O:39].C(=O)(O)[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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].O.ClCCl.C(#N)C>[NH2:35][C:36]1[C:44]([CH3:45])=[CH:43][C:42]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:12]3=[N:13][CH:14]=2)=[CH:41][C:37]=1[C:38]([OH:40])=[O:39]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 516892Sodium BicarbonateHCID 112312332-Amino-5-iodo-3-methylbenzoic 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 579758022-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acidYield 81%

Reagents, catalysts & solvents 4

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

650 mg (1.35 mmol) 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, 449 mg (1.35 mmol max.) of 2-amino-5-iodo-3-methyl-benzoic acid and 55 mg (67 μmol) of dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct were placed in a vial. 10 mL of acetonitrile and 10 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was closed and the mixture irradiated in a Personal Chemistry® Optimizer to 120° C. for 20 min. The crude mixture was distributed between dichloromethane and water, adjusting the pH to 4-5 by addition of 10% aqueous citric acid. The aqueous layer was extracted three times with ethyl acetate. The combined organic phases were washed with a saturated aqueous solution of sodium bromide, dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 551 mg (1.09 mmol, 81%) of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methyl-benzoic acid as a beige solid. MS: m/z 505.1 (M+H+), 528.1 (M+Na+).

Workup

  1. customThe vial was closed
  2. customthe mixture irradiated in a Personal Chemistry® Optimizer to 120° C. for 20 min
  3. extractionThe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic phases were washed with a saturated aqueous solution of sodium bromide
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5e6943c2dee54df9b9cf7723376c5258
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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