Sodium Bicarbonate → 6-[4-(Acetylamino)phenyl]-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

HRID 476021Notes

Reaction equation

HRID 476021 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.[C:28]([NH:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)(=[O:30])[CH3:29].COCCOC.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:28]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]3[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])=[O:16])[C:5]3[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=3[N:7]=2)=[CH:34][CH:33]=1)(=[O:30])[CH3:29]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 27346574-Acetamidophenylboronic acidHCID 18180031Water 1,2-dimethoxyethaneHCID 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 565988136-[4-(Acetylamino)phenyl]-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

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

The title compound was prepared in the same manner as described in example 93 using 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 (80 mg, 0.21 mmol), [4-(acetylamino)phenyl]boronic acid (55.4 mg, 0.31 mmol), bis(triphenylphosphine)palladium(II) chloride (8.4 mg, 0.01 mmol), DME/water (4 mL, 3:1) and sodium bicarbonate (52 mg, 0.62 mmol). The crude product was dissolved in DCM/MeOH (1:1) and preabsorbed onto silica gel. The product was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH. gradient of 0 to 80:20:2). The collected solid was suspended in EtOH/EtOAc (1:1), sonicated, and filtered. After further washing with hexanes, the solid was then air-dried for 15 min, and then in vacuum oven overnight. The final product was collected as 70 mg (69%). LCMS E-S (M+H)=487.3 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (br. s., 1H) 10.16 (s, 1H) 8.73 (t, J=5.05 Hz, 1H) 8.17 (m, J=8.84 Hz, 2H) 7.74 (m, J=8.84 Hz, 2H) 7.64 (s, 1H) 5.89 (s, 1H) 5.25 (quin, J=6.69 Hz, 1H) 4.39 (d, J=4.80 Hz, 2H) 2.43 (s, 3H) 2.25 (s, 3H) 2.12 (s, 3H) 2.09 (s, 3H) 1.51 (s, 3H) 1.49 (s, 3H).

Workup

  1. custompreabsorbed onto silica gel
  2. customThe product was purified by silica gel chromatography (eluent: DCM/MeOH/NH4OH. gradient of 0 to 80:20:2)
  3. customsonicated
  4. filtrationfiltered
  5. washAfter further washing with hexanes
  6. customthe solid was then air-dried for 15 min
  7. customin vacuum oven overnight
  8. customThe final product was collected as 70 mg (69%)

Sources & evidence

ORD record
ord-a918108ee09b426a93ac848a004ff49b
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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