Dichloromethane → 4-[3-(2-Methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N-methyl-benzamide

HRID 2388950Notes

Reaction equation

HRID 2388950 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][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:19][NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22].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:26]3[CH:27]=[CH:28][C:23]([C:21]([NH:20][CH3:19])=[O:22])=[CH:24][CH:25]=3)[CH:3]=2)[NH:8][N:9]=1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 178489372HCID 178489372, compound

Product 1

HCID 1784852994-[3-(2-Methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N-methyl-benzamideYield 20%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
130 °C

Procedure

To a solution of 5-bromo-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridine (26 mg, 0.085 mmol) in acetonitrile (1 mL) and saturated aqueous NaHCO3 (1 mL) in a microwave vial was added 4-(N-methylaminocarbonyl)phenylboronic acid (17 mg, 0.094 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (1:1) (3.5 mg, 0.004 mmol). The vial was capped, flushed with N2, evacuated under vacuum, and heated in a microwave at 130° C. for 1800 seconds. The material was extracted into EtOAc and the organic layer was dried over Na2SO4. The material was adsorbed onto SiO2 and purified by flash chromatography in a EtOAc (containing 10% MeOH) and hexane gradient. The clean fractions were concentrated via rotary evaporation to afford the title compound as a white powder (5.9 mg, 20% yield). 1H NMR (500 MHz, CD3OD) δ 8.85 (s, 1H), 8.41 (s, 1H), 7.94 (d, J=8.5 Hz, 2H), 7.78 (d, J=8.5 Hz, 2H), 7.67 (d, J=7.5 Hz, 1H), 7.48 (t, 7.0 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 7.11 (t, J=7.0 Hz, 1H), 3.89 (s, 3H), 2.95 (s, 3H). MS: m/z 359.1 [M+H+].

Workup

  1. customThe vial was capped
  2. customflushed with N2
  3. customevacuated under vacuum
  4. extractionThe material was extracted into EtOAc
  5. dry with materialthe organic layer was dried over Na2SO4
  6. custompurified by flash chromatography in a EtOAc (containing 10% MeOH) and hexane gradient
  7. concentrationThe clean fractions were concentrated via rotary evaporation

Sources & evidence

ORD record
ord-886eab00f2734f0cbb3948fa708740f5
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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