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

HRID 404Notes

Reaction equation

HRID 404 reaction equation
COc1nc(N)ccc1-n1cnc(C)c1.Cc1csc(C2CN(C)Cc3ccc(Cl)nc3O2)n1>CC(=O)O.CC(=O)O.COCCOC.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1>COc1nc(Nc2ccc3c(n2)OC(c2nc(C)cs2)CN(C)C3)ccc1-n1cnc(C)c1

Participants

7

Reactant 2

HCID 534029676-Methoxy-5-(4-methyl-1H-imidazol-1-YL)pyridin-2-amineHCID 575128718-Chloro-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine

Product 1

HCID 57512830N-(6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineYield 20.42%

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-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (50 mg, 0.17 mmol) in DME (3 mL) were 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (34.5 mg, 0.17 mmol), cesium carbonate (83 mg, 0.25 mmol), 2-(Dicyclohexylphosphino)biphenyl (5.92 mg, 0.02 mmol) and Palladium acetate (3.80 mg, 0.02 mmol) added. The reaction was heated to 110°C for 90 min under N2 atmosphere. The solids were filtered off and washed with DCM, the solvents were evaporated and the crude product was purified by silica flash chromatography, MeOH, 0-10%, in DCM yielding N-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (16.00 mg, 20.42 %)

Sources & evidence

ORD record
ord-53ade929d04044c58b3188ce55627881
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

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