Toluene → HCID 70979482, compound

HRID 1485453Notes

Reaction equation

HRID 1485453 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[C@H:9]([CH3:16])[CH2:8][N:7]([C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[C:6]=2[CH:25]=1.CC1([CH2+])C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37](=[O:40])[NH:36][CH:35]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>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.C(O)C>[CH3:15][C:12]1[N:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:34]4[CH:39]=[CH:38][C:37](=[O:40])[NH:36][CH:35]=4)=[CH:25][C:6]=3[N:7]([C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[CH2:8][C@@H:9]([CH3:16])[C:10]2=[N:14][N:13]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 70979774HCID 70979774, compoundHCID 86718506HCID 86718506, compound

Product 1

HCID 70979482HCID 70979482, compoundYield 49%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-4-(8-bromo-1,4-dimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-6(5H)-yl)benzonitrile (39.3 mg, 0.1 mmol), (4,5,5-trimethyl-2-(6-oxo-1,6-dihydropyridin-3-yl)-1,3,2-dioxaborolan-4-yl) methylium (66 mg, 0.3 mmol, tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol), cesium carbonate (65.2 mg, 0.2 mmol), toluene (2 mL), ethanol (1 mL) and water (3 drops) was stirred at 100° C. for 16 hours. The mixture was diluted with water (5 mL) and extracted with ethyl acetate (3*20 mL). The combined organic layers were washed with water (3*20 mL), brine (3*20 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo, and the residue was purified by column chromatography (silica gel, dichloromethane/methanol=15:1) to give (R)-4-(1,4-dimethyl-8-(6-oxo-1,6-dihydropyridin-3-yl)-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-6(5H)-yl)benzonitrile as a white solid (20 mg, 49.0%).

Workup

  1. extractionextracted with ethyl acetate (3*20 mL)
  2. washThe combined organic layers were washed with water (3*20 mL), brine (3*20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was purified by column chromatography (silica gel, dichloromethane/methanol=15:1)

Sources & evidence

ORD record
ord-6115f0a9fd2143d2aaf6f9e21c86020e
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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