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

HRID 1485459Notes

Reaction equation

HRID 1485459 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:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=3)[C:6]=2[CH:24]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[CH:35][C:36](=[O:39])[NH:37][CH:38]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([N:7]2[CH2:8][C@@H:9]([CH3:16])[C:10]3=[N:14][N:13]=[C:12]([CH3:15])[N:11]3[C:5]3[CH:4]=[CH:3][C:2]([C:33]4[CH:34]=[CH:35][C:36](=[O:39])[NH:37][CH:38]=4)=[CH:24][C:6]2=3)=[N:18][CH:19]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 177502535-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-olHCID 70979392(R)-8-bromo-6-(5-chloropyridin-2-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 70978807(R)-5-(6-(5-chloropyridin-2-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2(1H)-oneYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

To a solution of (R)-8-bromo-6-(5-chloropyridin-2-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (100 mg, 0.24 mmol) in 1,4-dioxane/H2O (10:1, 2 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (65 mg, 0.29 mmol), Cesium carbonate (156 mg, 0.48 mmol) and Tetrakis(triphenylphosphine)palladium(0) (18.4 mg, 0.025 mmol). The mixture was purged with N2 and stirred in the microwave at 130° C. for 0.5 hr. After filtration, concentrated in vacuo and purification by prep-TLC (elute: DCM:MeOH=15:1) gave (R)-5-(6-(5-chloropyridin-2-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2(1H)-one (30 mg, 30%).

Workup

  1. customThe mixture was purged with N2
  2. filtrationAfter filtration
  3. concentrationconcentrated in vacuo and purification by prep-TLC (elute: DCM:MeOH=15:1)

Sources & evidence

ORD record
ord-7656afa34ea4445d9490cede29f5f864
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

Loading…