Water → HCID 56597292, compound

HRID 1522383Notes

Reaction equation

HRID 1522383 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[NH2:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C(=O)(O)[O-].[Na+].O>COCCOC.O.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].C(Cl)Cl>[NH2:27][C:28]1[CH:33]=[C:32]([C:2]2[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=3[CH3:24])=[O:15])[C:5]3[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=3[N:7]=2)[CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 962WaterHCID 922693-Aminophenylboronic acidHCID 516892Sodium BicarbonateHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56597292HCID 56597292, compoundYield 44.2%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (80 mg, 0.21 mmol) and (3-aminophenyl)boronic acid (46.9 mg, 0.34 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.74 mg, 0.01 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (53.9 mg, 0.64 mmol) was added, the vessel was sealed, and the reaction mixture was irradiated (microwave) at 150° C. for 25 min. After cooling, 2 mL of water was added to the black mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added, the mixture was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with EtOH/EtOAc/hexanes (1:1:1). The solids that precipitated were filtered and dried to afford the title compound (40 mg, 42%) as a light grey solid. LCMS E-S (M+H)=431.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (br. s., 1 H), 8.96 (t, J=4.93 Hz, 1 H), 8.34 (s, 1 H), 8.02 (s, 1 H), 7.46 (t, J=1.89 Hz, 1 H), 7.36 (d, J=7.58 Hz, 1 H), 7.18 (t, J=7.71 Hz, 1 H), 6.69 (dd, J=7.83, 1.52 Hz, 1 H), 5.90 (s, 1 H), 5.25-5.37 (m, 3 H), 4.40 (d, J=4.80 Hz, 2 H), 2.22 (s, 3 H), 2.13 (s, 3 H), 1.55 (s, 3 H), 1.54 (s, 3 H).

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. customthe reaction mixture was irradiated (microwave) at 150° C. for 25 min
  5. temperatureAfter cooling
  6. customthat precipitated
  7. filtrationwere filtered
  8. additionDCM/MeOH (1:1) was added
  9. customthe mixture was pre-absorbed on silica gel
  10. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  11. additionThe isolated product was treated with EtOH/EtOAc/hexanes (1:1:1)
  12. customThe solids that precipitated
  13. filtrationwere filtered
  14. customdried

Sources & evidence

ORD record
ord-83d3b3f114624768803dd02d264435f8
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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