5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine → 5-Fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine

HRID 19

Reaction equation

HRID 19 reaction equation
Cc1ncc(-c2nc(N)ncc2F)n1C1CCOCC1.Fc1cc(CN2CCOCC2)ccc1Br>CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.CCC(C)(C)[O-].Cc1ccccc1.[Na+].[Pd]>Cc1ncc(-c2nc(Nc3ccc(CN4CCOCC4)cc3F)ncc2F)n1C1CCOCC1

Participants

7

Reactant 2

HCID 166654985-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amineHCID 534178184-(4-Bromo-3-fluorobenzyl)morpholine

Product 1

HCID 497820135-Fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amineYield 85%

Reagents, catalysts & solvents 4

HCID 2733478Sodium 2-methylbutan-2-olateReagentHCID 23938PalladiumCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

The aim of the reaction is test/optimization: 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (100 mg, 0.36 mmol), 4-(4-bromo-3-fluorobenzyl)morpholine (109 mg, 0.40 mmol), Palladium, 10% On Charcoal (115 mg, 0.11 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (94 mg, 0.16 mmol) and Sodium tert-pentoxide (79 mg, 0.72 mmol) were dissolved in toluene (1.5 mL) and heated to 110 °C under argon. The reaction was monitorred by HPLC. After 16 h 85 % conversion was achieved. The reaction was stopped and the mixture was discarded.

Sources & evidence

ORD record
ord-ea29507936c14849a1aa88403efb7090
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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