Reaction equation
CC(C)N1CCNCC1.CCOC(=O)c1cnc2cc(OCC)c(Br)cc2c1Nc1ccc(F)cc1F>O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C([O-])[O-].[Cs+].[Cs+].[Pd].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>CCOC(=O)c1cnc2cc(OCC)c(N3CCN(C(C)C)CC3)cc2c1Nc1ccc(F)cc1FParticipants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 110 °C
Procedure
To a solution of ethyl 6-bromo-4-(2,4-difluorophenylamino)-7-ethoxyquinoline-3-carboxylate (400 mg, 0.89 mmol) and 1-(Isopropyl)piperazine (254 µl, 1.77 mmol) in dioxane was added cesium carbonate (722 mg, 2.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (40.6 mg, 0.04 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (55.2 mg, 0.09 mmol). Reaction vessel in oil bath set to 110 °C. 11am After 5 hours, MS shows product (major peak 499), and SM (minor peak 453). o/n, MS shows product peak. Reaction cooled, concentrated onto silica, and purified on ISCO. 40g column, 1:1 EA:Hex, then 100% EA. 289mg yellow solid. NMR (EN00180-62-1) supports product, but some oxidised BINAP impurity (LCMS 655).
Sources & evidence
- ORD record
- ord-56b1f4bfeebc4b8ab990b9804e798aa7
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Linked notes
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