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Buchwald–Hartwig amination: 8-Chloro-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine → N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

73% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below.

verified record, 73% yield recorded, Not balanced as written, From experimental reaction archive

Reagents, catalysts and solvents are in the table below.

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The atoms, from reactants to products

COCNCNCCCCCNOCCNCCCSCCNCCCCCCCNNCCCl
Reactants · 1/6
breakingformingbond order changesmapped atom that changes

Drawn from the record's atom map: which bonds break and which form between the reactants and products the source listed. It shows a change in connectivity, not a simulated trajectory and not a mechanism.

What was in the flask

RoleSpeciesFormulaYield
Reactant8-Chloro-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepineC₁₄H₁₆ClN₃OS—
Reactant6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-ylamineC₁₀H₁₂N₄O—
ReagentCesium carbonateCCs₂O₃—
Catalyst2-(Dicyclohexylphosphino)biphenylC₂₄H₃₁P—
CatalystPalladium (II) acetateC₄H₈O₄Pd—
Solvent1,2-DimethoxyethaneC₄H₁₀O₂—
ProductN-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amineC₂₄H₂₇N₇O₂S73.35%

The equation does not balance as written. That is usual for an experimental record: the source listed what it put in and what it measured, not a stoichiometric equation.

Conditions

Temperature
110 °C

Only the dimensions the source stated are listed. Anything absent here was not recorded, and it is not inferred from what the class usually needs.

Yield

  • 73% of N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine.

Other recorded runs with the same starting material

No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.

Procedure

Copied from the source record, unedited

To 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.086 g, 0.42 mmol) in DME (3 mL) were 8-chloro-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.130 g, 0.42 mmol), cesium carbonate (0.205 g, 0.63 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.015 g, 0.04 mmol) and Palladium acetate (9.42 mg, 0.04 mmol) added. The reaction was heated to 110°C for 60 min under argon atmosphere. The reaction mixture was filtered through celite, washed with DCM and the solvents were evaporated. The crude product was purified by silica flash chromatography, MeOH, 0-5%, in DCM yielding N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.147 g, 73.4 %). The product was subm

The source

This record comes from experimental reaction archive (ord-127ed8ac0e574ba4a6f68accaf8c96d2). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-127ed8ac0e574ba4a6f68accaf8c96d2 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.

    experimental record · quality medium · source

experimental reaction record.

How to read this record

This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.

The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.

Where to next

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