4-(4-Bromobenzyl)morpholine → 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine

HRID 53

반응식

HRID 53 반응식
Brc1ccc(CN2CCOCC2)cc1.Cc1ncc(-c2nc(N)ncc2F)n1C1CCOCC1>C1COCCO1.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.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]>Cc1ncc(-c2nc(Nc3ccc(CN4CCOCC4)cc3)ncc2F)n1C1CCOCC1

참가 물질

7

반응물 2

HCID 7835034-(4-Bromobenzyl)morpholineHCID 166654985-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine

생성물 1

HCID 166652515-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine수율 85.5%

시약·촉매·용매 4

HCID 10796Cesium carbonate시약HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

The aim of the reaction is optimization. Tris(dibenzylideneacetone)dipalladium(0) (4.5 mg, 4.91 µmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (5.1 mg, 8.81 µmol) were dissolved in dioxane (1.8 mL) in a 10 mL Schlenk tube and activated at 100 °C for 6 min under argon. Then 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (51 mg, 0.18 mmol), 4-(4-bromobenzyl)morpholine (51 mg, 0.20 mmol) and Cesium carbonate (94 mg, 0.29 mmol) were added. It was degassed again and stirred at 100 °C under argon. The reaction was followed by HPLC. After 26 h 85.5 % conversion was obtained. 20 % by-product formation was detected. Finally, the reaction mixture was discarded.

출처 및 근거

ORD 기록
ord-f88e9fa13a294cdea3238d7489919aa6
출처 데이터셋
750 AstraZeneca ELN dataset
원본 링크
출처 보기

연결된 노트

불러오는 중…