Cesium carbonate → 4-(8-methoxy-1,4-dimethyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-6(5H)-yl)benzonitrile

HRID 1485465Notes

Reaction equation

HRID 1485465 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]3[C:13]([CH3:16])=[N:14][N:15]=[C:11]3[CH:10]([CH3:17])[CH2:9][NH:8][C:7]=2[N:18]=1.I[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]3[C:13]([CH3:16])=[N:14][N:15]=[C:11]3[CH:10]([CH3:17])[CH2:9][N:8]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=3)[C:7]=2[N:18]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 764674-IodobenzonitrileHCID 709798778-methoxy-1,4-dimethyl-5,6-dihydro-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 709792804-(8-methoxy-1,4-dimethyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-6(5H)-yl)benzonitrileYield 31%

Reagents, catalysts & solvents 2

HCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 8-methoxy-1,4-dimethyl-5,6-dihydro-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepine (50 mg, 0.203 mmol) in toluene (2 mL) was added 4-iodobenzonitrile (94 mg, 0.406 mmol), Bis(dibenzylideneacetone) Palladium (28 mg, 0.03 mmol), 2-dicyclohexylphosphin-2′,6′-dimethoxybiphenyl (25 mg, 0.06 mmol) and cesium carbonate (132 mg, 0.406 mmol). The mixture was purged with N2 and stirred at 110° C. for 12 hours. The reaction mixture was washed with brine (5 mL), and then the mixture was filtered. The filtrate was extracted with acetic ester (10 mL×3), the combined organic phase was dried by anhydrous sodium sulphate, and then filtered. The filtrate was concentrated and purified by preparative HPLC (Mobile phase A: water with 0.05% ammonia solution; Mobile phase B: MeCN; column temperature: 30° C., Gradient: 30-60% B 10 min) to give 4-(8-methoxy-1,4-dimethyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-6(5H)-yl)benzonitrile (2.7 mg, 31%) as a colorless solid.

Workup

  1. customThe mixture was purged with N2
  2. washThe reaction mixture was washed with brine (5 mL)
  3. filtrationthe mixture was filtered
  4. extractionThe filtrate was extracted with acetic ester (10 mL×3)
  5. dry with materialthe combined organic phase was dried by anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. custompurified by preparative HPLC (Mobile phase A: water with 0.05% ammonia solution; Mobile phase B: MeCN; column temperature: 30° C., Gradient: 30-60% B 10 min)

Sources & evidence

ORD record
ord-a72153834a144c1e89d7c9719a0d03b8
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

Loading…