3-chloro-4-(1H-1,2,4-triazol-1-yl)aniline → (R)-2-(8-(3-Chloro-4-(1H-1,2,4-triazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol

HRID 277

Reaction equation

HRID 277 reaction equation
Nc1ccc(-n2cncn2)c(Cl)c1.OCCN1Cc2ccc(Cl)nc2O[C@H](c2ccccc2)C1>CC(=O)O.CC(=O)O.COCCOC.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>OCCN1Cc2ccc(Nc3ccc(-n4cncn4)c(Cl)c3)nc2O[C@H](c2ccccc2)C1

Participants

7

Reactant 2

HCID 163948663-chloro-4-(1H-1,2,4-triazol-1-yl)anilineHCID 59577824(R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol

Product 1

HCID 49818940(R)-2-(8-(3-Chloro-4-(1H-1,2,4-triazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanolYield 8.78%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 4144353Palladium (II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

3-chloro-4-(1H-1,2,4-triazol-1-yl)aniline (77 mg, 0.39 mmol), (R)-2-(8-chloro-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (120 mg, 0.39 mmol), Palladium acetate (8.84 mg, 0.04 mmol), 2-(Dicyclohexylphosphino)biphenyl (13.80 mg, 0.04 mmol)and Cesium carbonate (385 mg, 1.18 mmol) were added to a microwave vial. 1,2-dimethoxyethane (2 mL) and EtOH (0.500 mL) were added. The reaction mixture was flushed with argon and the mixture was run in a microwave for 60 minutes at 100°C. The solvent was decanted and the solids were washed with DCM, 5ml. The solvent was then evaporated and the crude product was purified on prepHPLC yielding (R)-2-(8-(3-chloro-4-(1H-1,2,4-triazol-1-yl)phenylamino)-2-phenyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4(5H)-yl)ethanol (16.00 mg, 8.78 %)

Sources & evidence

ORD record
ord-432ccffac1cc473eadf2f2e10de5f379
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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