Cesium carbonate → (R)-5-(1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amine

HRID 1485451Notes

Reaction equation

HRID 1485451 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:18]=[N:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=3)[C:6]=2[CH:26]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=2)O1.[F-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.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.C1(C)C=CC=CC=1>[CH3:15][C:12]1[N:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:35]4[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=4)=[CH:26][C:6]=3[N:7]([C:17]3[CH:18]=[N:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=3)[CH2:8][C@@H:9]([CH3:16])[C:10]2=[N:14][N:13]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 522689Potassium FluorideHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 70979064(R)-8-bromo-1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 70979691(R)-5-(1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amineYield 51.3%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (R)-8-bromo-1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (42 mg, 0.1 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (27 mg, 0.12 mmol), tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol), potassium fluoride (5.8 mg, 0.1 mmol) and cesium carbonate (49 mg, 0.15 mmol) in a mixed solution of toluene (2 mL), ethanol (1 mL) and water (0.2 mL) was heated at 110° C. for 1.5 hours under microwave (pressure: 3.0 bar, equipment power: 150 W). The reaction mixture was diluted with ethyl acetate (20 mL) and washed with brine (10 mL×3). The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to give a crude product (R)-5-(1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amine (22 mg, 51%) which was used in the next step without further purification.

Workup

  1. washwashed with brine (10 mL×3)
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-5d4a192b32344b4ba40464cadda5c528
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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