5-(4-Methyl-1H-imidazol-1-yl)pyridin-2-amine → (R)-4-Methyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

HRID 314

Reaction equation

HRID 314 reaction equation
CN1Cc2ccc(Cl)nc2O[C@H](c2ccccc2)C1.Cc1cn(-c2ccc(N)nc2)cn1>CC(=O)O.CC(=O)O.COCCOC.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>Cc1cn(-c2ccc(Nc3ccc4c(n3)O[C@H](c3ccccc3)CN(C)C4)nc2)cn1

Participants

7

Reactant 2

HCID 575128615-(4-Methyl-1H-imidazol-1-yl)pyridin-2-amineHCID 57512880(2R)-8-chloro-4-methyl-2-phenyl-3,5-dihydro-2H-pyrido[3,2-f][1,4]oxazepine

Product 1

HCID 57512832(R)-4-Methyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineYield 35.89%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

(R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (129 mg, 0.47 mmol), 5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (82 mg, 0.47 mmol), PALLADIUM(II) ACETATE (10.54 mg, 0.05 mmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (16.46 mg, 0.05 mmol) and Cs2CO3 (229 mg, 0.70 mmol) were weighed into a microwave vial which was capped and flushed with argon. DME (5 mL) was added and the mixture was heated to 100°C in a microwave apparatus for 2 h. The mixture was filtered and purified by column chromatography on Silica using gradient elution with increasing concentration of methanol, from 0 to 6 %, in dichloromethane to give(R)-4-methyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (69.5 mg, 35.9 %)

Sources & evidence

ORD record
ord-2bf055ae52c14e578ca506139e6af8cb
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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