Dichloromethane → HCID 178489390, compound

HRID 272039

Reaction equation

HRID 272039 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[N:9][N:8](COCC[Si](C)(C)C)[C:5]2=[N:6][CH:7]=1.[C:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)([OH:29])=[O:28].ClCCl>C(#N)C.C([O-])(O)=O.[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:18][O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:34]3[CH:35]=[C:30]([CH:31]=[CH:32][CH:33]=3)[C:27]([OH:29])=[O:28])[CH:3]=2)[NH:8][N:9]=1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 27339573-Carboxyphenylboronic acidHCID 598360325-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 178489390HCID 178489390, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (997 mg, 2.30 mmol) in acetonitrile (15 mL) and saturated aqueous NaHCO3 (10 mL) in a microwave vial was added 3-carboxyphenylboronic acid, pinacol ester (625 mg, 2.52 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (1:1) (94 mg, 0.12 mmol). The vial was capped, flushed with N2, evacuated under vacuum, and heated in a microwave at 90° C. for 1500 seconds. The acetonitrile was removed via rotary evaporation. Ethyl acetate was added and then separated from the aqueous layer. The organic layer was dark brown and LC/MS showed that the product remained in this layer. Concentrated down to a dark brown oil and redissolved in a 5% perchloric acid in acetic acid solution (10 mL). The reaction solution was stirred 4.5 hours at ambient temperature. The perchloric acid was removed via rotary evaporation and then ethyl acetate and H2O were added. Sodium bicarbonate powder was added until pH=3. The organic layer was separated, dried over Na2SO4, and concentrated under vacuum to afford a brown powder (580 mg, 62% yield). 1H NMR (500 MHz, d6-DMSO) δ 13.81 (br s, 1H), 8.81 (d, J=2.5 Hz, 1H), 8.31 (d, J=2.5 Hz, 1H), 8.18 (s, 1H), 7.95 (d, J=7.5 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 7.59 (m, 2H), 7.41 (t, J=7.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.5 Hz, 1H), 3.80 (s, 3H). MS: m/e 346.1 (M+H+).

Workup

  1. customThe vial was capped
  2. customflushed with N2
  3. customevacuated under vacuum
  4. customThe acetonitrile was removed via rotary evaporation
  5. additionEthyl acetate was added
  6. customseparated from the aqueous layer
  7. concentrationConcentrated down to a dark brown oil
  8. dissolutionredissolved in a 5% perchloric acid in acetic acid solution (10 mL)
  9. customThe perchloric acid was removed via rotary evaporation
  10. additionethyl acetate and H2O were added
  11. additionSodium bicarbonate powder was added until pH=3
  12. customThe organic layer was separated
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-26c8fb5585354a42ba2a77fe5cf8a6a3
Source dataset
uspto-grants-2008_11
Patent number
US07452993B2

Linked notes

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