Toluene → 2'-Cyano-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxamide

HRID 1845188Notes

Reaction equation

HRID 1845188 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:18]=1)[C:5]([NH:7][CH2:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=1)=[O:6].[CH3:26][C:27]1[CH:28]=[CH:29][C:30](B2OC(C)(C)C(C)(C)O2)=[C:31]([CH:34]=1)[C:32]#[N:33].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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.O.C(O)C>[C:32]([C:31]1[CH:34]=[C:27]([CH3:26])[CH:28]=[CH:29][C:30]=1[C:2]1[CH:18]=[C:17]([C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[C:4]([C:5]([NH:7][CH2:8][C:9]2[CH:10]=[N:11][C:12]([CH3:15])=[N:13][CH:14]=2)=[O:6])[CH:3]=1)#[N:33]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 581880073-Bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamideHCID 584073295-Methyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 442230412'-Cyano-4'-methyl-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Into a Parr pressure reactor were charged 3-bromo-N-((2-methylpyrimidin-5-yl)methyl)-5-(pyrrolidine-1-carbonyl)benzamide (240 mg, 0.48 mmol), 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (160 mg, 0.58 mmol) (WO 2008/130481), toluene (5 mL), ethanol (1 mL), cesium carbonate (170 mg, 0.52 mmol), and water (0.5 mL). The mixture was degassed and purged with nitrogen several times and then tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol) was added. The tube was sealed and the mixture was heated at 90° C. overnight. After cooling, the mixture was filtered through Celite and the filtrate was concentrated. The residue was purified via flash chromatography and then preparative HPLC to afford the desired product as a white solid.

Workup

  1. customThe mixture was degassed
  2. custompurged with nitrogen several times
  3. customThe tube was sealed
  4. temperatureAfter cooling
  5. filtrationthe mixture was filtered through Celite
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified via flash chromatography

Sources & evidence

ORD record
ord-c778e4b7bccd4dbdb97bea296dc4abc4
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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