(2R)-8-chloro-4-methyl-2-phenyl-3,5-dihydro-2H-pyrido[3,2-f][1,4]oxazepine → (R)-N-(3-Methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

HRID 229

Reaction equation

HRID 229 reaction equation
CN1Cc2ccc(Cl)nc2O[C@H](c2ccccc2)C1.COc1cc(N)ccc1-n1cnc(C)n1>CC(=O)O.CC(=O)O.CCO.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>COc1cc(Nc2ccc3c(n2)O[C@H](c2ccccc2)CN(C)C3)ccc1-n1cnc(C)n1

Participants

7

Reactant 2

HCID 57512880(2R)-8-chloro-4-methyl-2-phenyl-3,5-dihydro-2H-pyrido[3,2-f][1,4]oxazepineHCID 595778183-Methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline

Product 1

HCID 49819232(R)-N-(3-Methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineYield 18.97%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 4144353Palladium (II) acetateCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

(R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (180 mg, 0,66 mmol), 3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (134 mg, 0,66 mmol), Palladium acetate (14,71 mg, 0,07 mmol), 2-(Dicyclohexylphosphino)biphenyl (22,96 mg, 0,07 mmol) and Cesium carbonate (640 mg, 1,97 mmol) were mixed in DME (3 mL) in a microwave vial. EtOH (0,3 mL) was added and the mixture was run for 1 hour at 100°C in a microwave reactor. the reaction had to be run for an additional 2 hours with more catalyst and ligand added. the mixture was filtered and purified using flash chromatography 0-10% MeOH in DCM.

Sources & evidence

ORD record
ord-f1632d43480c447bab6a25aa93c74396
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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