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Buchwald–Hartwig amination: (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine → (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine

0% yield, run at 120 °C, as recorded by experimental reaction archive. The written procedure is below. One of 7 recorded runs making this product; all of them are compared below.

verified record, 0% 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

COCCCNCNCCCNOCCCCCCCCNCCCCCNCNCCCCl
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
Reactant(R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepineC₁₄H₁₄ClN₃O—
Reactant3-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineC₁₁H₁₃N₃O—
ReagentPotassium CarbonateCK₂O₃—
CatalystBinap, (A+-)-C₄₄H₃₂P₂—
CatalystPalladium (II) acetateC₄H₈O₄Pd—
SolventTolueneC₇H₈—
Product(R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amineC₂₅H₂₆N₆O₂0%

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
120 °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

  • 0% of (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine.

Every recorded run making this product

7 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.

CatalystReagentsSolventTemp.TimeYield
1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetateCesium carbonate1,4-Dioxane130 °C—30%
Tris(1,1-dimethylethyl)phosphine; Palladium (II) acetateCesium carbonate1,4-Dioxane120 °C—15%
2-(Dicyclohexylphosphino)biphenyl; Palladium (II) acetateCesium carbonate1,2-Dimethoxyethane100 °C—7%
Binap, (A+-)-; Palladium (II) acetatePotassium CarbonateToluene120 °C—0% (this run)
Tris(1,1-dimethylethyl)phosphine; Palladium (II) acetateSodium 2-methylbutan-2-olate1,4-Dioxane120 °C—0%
Binap, (A+-)-; Bis(dibenzylideneacetone)palladiumsodium 2-methylpropan-2-olateToluene120 °C—0%
1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladiumCesium carbonate1,4-Dioxane130 °C—0%

Every value is as the source recorded it. A run with no yield was reported without one, and nothing here is averaged, modelled or filled in.

Procedure

Copied from the source record, unedited

Purpose: to examine scale-up of microwave conditions established in a previous experiment. Charged a round-bottom flask with a mixture of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.702 g, 3.45 mmol), (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (1.0 g, 3.63 mmol), palladium (II) acetate (0.023 g, 0.10 mmol), rac-BINAP (0.108 g, 0.17 mmol), potassium carbonate (0.716 g, 5.18 mmol), and toluene (20 mL). The atmosphere s inerted through nitrogen purge cycles, then heated at 120 °C or 16 hours. HPLC-UV shows the reaction is not as clean as in the microwave, and conversion is very poor. The contents were allowed to continue heating over the weekend, but although conversion improved, the mixture contained many impurities. Not progressed. name='[Samples]

The source

This record comes from experimental reaction archive (ord-b814b75406f3451f844066ae5ac468ab). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-b814b75406f3451f844066ae5ac468ab 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

More Buchwald–Hartwig amination records

Other runs of this class, one page per distinct transformation.

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Buchwald–Hartwig amination → (R)-N-(3-methoxy-4-(4-methyl-1H-…