Water → HCID 68079117, compound

HRID 1522384Notes

Reaction equation

HRID 1522384 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.[C:27]([NH:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)(=[O:29])[CH3:28].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>[C:27]([NH:30][C:31]1[CH:36]=[C:35]([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:34]=[CH:33][CH:32]=1)(=[O:29])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 157274(3-Acetamidophenyl)boronic 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 68079117HCID 68079117, compoundYield 65.5%

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-(acetylamino)phenyl]boronic acid (57.5 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.7 mg, 0.010 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 30 min. After cooling, 2 mL of water was added 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 and DCM, filtered, and dried to afford the title compound (65 mg, 63%) as a white solid. LCMS E-S (M+H)=473.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (s, 1 H), 9.02 (t, J=4.80 Hz, 1 H), 8.61-8.68 (m, 2 H), 8.37-8.43 (m, 2 H), 8.21 (s, 1 H), 7.94 (d, J=7.83 Hz, 1 H), 7.65 (t, J=7.83 Hz, 1 H), 5.91 (s, 1 H), 5.37 (quin, J=6.63 Hz, 1 H), 4.42 (d, J=4.80 Hz, 2 H), 2.84 (d, J=4.29 Hz, 3 H), 2.24 (s, 3 H), 2.13 (s, 3 H), 1.57 (s, 3 H), 1.55 (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 30 min
  5. temperatureAfter cooling
  6. customsolids that 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 and DCM
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-8c29b01f6b8343afb62a122786dd9aa4
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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