Water → HCID 71543548, compound

HRID 1522519Notes

Reaction equation

HRID 1522519 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.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>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=[C:2]([C:30]2[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=2)[CH:3]=1)=[O:16]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 565974266-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 71543548HCID 71543548, compoundYield 78.8%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

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]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (90 mg, 0.23 mmol) and 3-pyridinylboronic acid (42.8 mg, 0.35 mmol) in dioxane/water (3:1 mL). PdCl2(dppf)-CH2Cl2 adduct (9.47 mg, 0.012 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium carbonate (58.5 mg, 0.7 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave to 110° C. for 20 min. Upon cooling, water was added and solids that precipitated were filtered, dissolved in DCM and purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The product containing fractions were evaporated and suspended in EtOH/EtOAc (1:1). The contents were sonicated, solids that precipitated were filtered, washed with hexanes and dried to afford the title compound as a white solid (78 mg, 77%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (br. s., 1 H) 9.39 (d, J=1.52 Hz, 1 H) 8.76 (t, J=5.05 Hz, 1 H) 8.69 (dd, J=4.67, 1.64 Hz, 1 H) 8.57 (dt, J=8.27, 1.80 Hz, 1 H) 7.78 (s, 1 H) 7.57 (dd, J=8.08, 5.56 Hz, 1 H) 5.89 (s, 1 H) 5.28 (quin, J=6.69 Hz, 1 H) 4.41 (s, 1 H) 4.39 (s, 1 H) 2.46 (s, 3 H) 2.25 (s, 3 H) 2.12 (s, 3 H) 1.52 (s, 3 H) 1.51 (s, 3 H); LC-MS (ES) m/z=431.1 [M+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. temperatureUpon cooling
  5. customsolids that precipitated
  6. filtrationwere filtered
  7. dissolutiondissolved in DCM
  8. custompurified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
  9. additionThe product containing fractions
  10. customwere evaporated
  11. customThe contents were sonicated
  12. customsolids that precipitated
  13. filtrationwere filtered
  14. washwashed with hexanes
  15. customdried

Sources & evidence

ORD record
ord-95c7f7d86ef84f219134c1d1d67bf3c7
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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