N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide → N-Cyclopropyl-3-(1-(2,6-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-4-methylbenzamide

HRID 2261254Notes

Reaction equation

HRID 2261254 reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]([CH3:9])[C:5]2[N:10]([C:13]3[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=3[F:20])[N:11]=[CH:12][C:4]=2[CH:3]=1.[CH:21]1([NH:24][C:25](=[O:43])[C:26]2[CH:31]=[C:30](B3OC(C)(C)C(C)(C)O3)[C:29]([CH3:41])=[C:28]([F:42])[CH:27]=2)[CH2:23][CH2:22]1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:21]1([NH:24][C:25](=[O:43])[C:26]2[CH:27]=[C:28]([F:42])[C:29]([CH3:41])=[C:30]([C:2]3[C:7](=[O:8])[N:6]([CH3:9])[C:5]4[N:10]([C:13]5[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=5[F:20])[N:11]=[CH:12][C:4]=4[CH:3]=3)[CH:31]=2)[CH2:22][CH2:23]1

Participants

7

Reactant 2

HCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 461976915-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

Product 1

HCID 25118571N-Cyclopropyl-3-(1-(2,6-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-4-methylbenzamideYield 66.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one (110 mg, 0.32 mmol), N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (122 mg, 0.38 mmol) and 15 mg of Pd(PPh3)4 in 2.0 mL dioxane and 0.8 mL of 1 M Na2CO3 in a sealed glass tube was heated at 130° C. for 30 min. The reaction mixture was diluted in EtOAc, washed with 1 N NaOH solution. The organic phase was dried over MgSO4, filtered and concentrated. Purification of the brown residue on an ISCO 12 g column (40-80% EtOAc in Hexanes) afforded the title compound (96 mg) as an off white amorphous solid. MS (ESI, pos.ion) m/z: 453.1 (M+1).

Workup

  1. washwashed with 1 N NaOH solution
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the brown residue on an ISCO 12 g column (40-80% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-3930e88edcf24db993585f24beec4d98
Source dataset
uspto-grants-2010_12
Patent number
US07846944B2

Reaction notes

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