2-(3-Bromophenyl)-2-hydroxyacetic acid → hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid

HRID 886616Notes

Reaction equation

HRID 886616 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]C(=O)C(C)(C)C)[N:10]=1.Br[C:36]1[CH:37]=[C:38]([CH:42]([OH:46])[C:43]([OH:45])=[O:44])[CH:39]=[CH:40][CH:41]=1>C1COCC1.C(#N)C.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]>[OH:46][CH:42]([C:38]1[CH:39]=[CH:40][CH:41]=[C:36]([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][OH:28])[C:12]3=[N:13][CH:14]=2)[CH:37]=1)[C:43]([OH:45])=[O:44]

Participants

5

Reactant 2

HCID 27570282-(3-Bromophenyl)-2-hydroxyacetic acidHCID 598250492,2-Dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

Product 1

HCID 59825038hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acidYield 43.2%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,2-dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (4.5 g, 9.7 mmol), (±)-(3-bromo-phenyl)-hydroxy-acetic acid (2.7 g, 11.6 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (355 mg, 0.5 mmol) in THF/Acetonitrile/saturated NaHCO3 (20 ml/20 ml/50 ml) was stirred at 100° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. The crude was purified by reverse phase HPLC afforded hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid (1.7 g, 35% yield). 1H NMR (500 MHz, DMSO-d6) δ 3.86 (s, 3H), 5.05 (s, 1H), 5.14 (s, 2H), 7.10 (m, 1H), 7.21 (d, 1H), 7.40-7.50 (m, 3H), 7.67 (d, 1H), 7.79 (s, 1H).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. extractionThe combined organic layers were extracted with brine
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness
  7. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3e7e924b1bb3480a8ac5657fbf318114
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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