8-Chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine → 4,6-Dimethyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

HRID 315

Reaction equation

HRID 315 reaction equation
Cc1cc(Cl)nc2c1CN(C)CC(CC(F)(F)F)O2.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(Nc3cc(C)c4c(n3)OC(CC(F)(F)F)CN(C)C4)nc2)cn1

Participants

7

Reactant 2

HCID 575128608-Chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepineHCID 575128615-(4-Methyl-1H-imidazol-1-yl)pyridin-2-amine

Product 1

HCID 575128254,6-Dimethyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineYield 15.45%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
110 °C

Procedure

To 8-chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (300 mg, 0.51 mmol) in DME (4 mL) were 5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (89 mg, 0.51 mmol), cesium carbonate (249 mg, 0.76 mmol), 2-(Dicyclohexylphosphino)biphenyl (17.84 mg, 0.05 mmol) and Palladium acetate (11.43 mg, 0.05 mmol) added. The reaction was heated to 110°C for 3*90min. The solids were filtered of and washed with DCM and IPA and discarded. The solvents were evaporated and the crude product was purified using first flash chromatography, 0-7% MeOH in DCM and the prepHPLC yielding 4,6-dimethyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (34.0 mg, 15.45 %)

Sources & evidence

ORD record
ord-6df914594aae4a42ba5b1bcb65424482
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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