Buchwald–Hartwig amination: (6S)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-8-one → (1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acid
16% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 recorded runs making this product; all of them are compared below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | (6S)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-8-one | C₂₀H₁₈ClF₂N₅O₂ | |
| Reactant | 2-Methyl-2H-pyrazol-3-ylamine | C₄H₇N₃ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Product | (1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acid | C₂₂H₂₂F₄N₂O₄ | 15.7% |
Conditions
- Temperature
- 110 °C
Yield
- 16% of (1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acid.
Every recorded run making this product
2 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.
| Reactants | Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|---|
| 2-[(5-Bromo-3-methoxy-2-pyridinyl)carbonyl]cyclopropanecarboxylic acid ethyl ester; 2-fluoro-N-(2-methylpropyl)-5-(trifluoromethyl)aniline | Binap, (A+-)-; Palladium (II) acetate | Cesium carbonate | Toluene | 110 °C | — | 29% |
| (6S)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-8-one; 2-Methyl-2H-pyrazol-3-ylamine | Binap, (A+-)-; Palladium (II) acetate | Cesium carbonate | 110 °C | — | 16% (this run) |
Procedure
Copied from the source record, unedited
18-mar-2014 17:15:52 +0100, blandar allt, add toluen, N2 flushar - rör 110 gC/ön/N2. Nästa em kl 16, fått svalna - LCMS ser bra ut, 17:49:27 - nu hydrolys/rt, klart efter 90 min ca, slår på 600 uL HoAc, evap. Till SSL, 24-mar-2014 190 mg åter från SSL. ( 1 g CBA prekond MeOH, löser i några ml ACN, eluerar mha 2.5 överkolonn vol, späder med avjonat aq, lyoph ön) HNMR OK LCMS OK
The source
This record comes from experimental reaction archive (ord-81f0402c864a4618afac454715899838). Open the source and check it against what is on this page.
experimental reaction archive record ord-81f0402c864a4618afac454715899838 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.
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.
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