6-Methoxy-5-(4-methyl-1H-imidazol-1-YL)pyridin-2-amine → (R)-N-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

HRID 514Notes

Reaction equation

HRID 514 reaction equation
CN1Cc2ccc(Cl)nc2O[C@H](c2ccccc2)C1.COc1nc(N)ccc1-n1cnc(C)c1>CC(=O)O.CC(=O)O.COCCOC.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>COc1nc(Nc2ccc3c(n2)O[C@H](c2ccccc2)CN(C)C3)ccc1-n1cnc(C)c1

Participants

7

Reactant 2

HCID 534029676-Methoxy-5-(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 49765107(R)-N-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineYield 15.63%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

A solution of (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (83 mg, 0.30 mmol) and 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (62.0 mg, 0.30 mmol) in DME (3 mL) was added to a microwave vial containing palladium(II) acetate (6.82 mg, 0.03 mmol), 2-(Dicyclohexylphosphino)biphenyl (10.64 mg, 0.03 mmol) and CS2CO3 (297 mg, 0.91 mmol) under an athmosphere of argon. The resulting mixture was heated to 100°C in a microwave apparatus for 2 h. The reaction mixture was diluted with dichloromethane and methanol and filtered through a plug of Celite. The solvents were evaporated and the residue was purified by HPLC to give 21 mg of the title product (16 % Yield).

Sources & evidence

ORD record
ord-88ebd75900f542a9b6cc4c328b0f3d84
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

Loading…