2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone

온도

120 °C

1-((2S,4R)-4-Amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 7) (150 mg, 0.457 mmol), 2-chloro-5-methylpyrazine (147 mg, 1.142 mmol), Davephos (71.9 mg, 0.183 mmol), Pd2(dba)3 (84 mg, 0.091 mmol) and sodium tert-butoxide (132 mg, 1.370 mmol) were combined in 1,4-dioxane (4 ml) and the mixture heated at 120° C. for 25 min (microwave). The reaction mixture was partitioned between water (75 ml) and DCM (3×75 ml). The organics were combined, dried (hydrophobic frit) and evaporated under vacuum. The resulting brown oil was dissolved in DMSO (3×1 ml) and purified by MDAP (formate ×3). The solvent was evaporated under vacuum to give 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (91 mg, 0.216 mmol, 47% yield) as a yellow glass. LCMS (formate), Rt 0.75 min, MH+ 421.

1. customThe reaction mixture was partitioned between water (75 ml) and DCM (3×75 ml)
2. customdried (hydrophobic frit)
3. customevaporated under vacuum
4. dissolutionThe resulting brown oil was dissolved in DMSO (3×1 ml)
5. custompurified by MDAP (formate ×3)
6. customThe solvent was evaporated under vacuum

ORD 기록

ord-1d79a20fe4254a369584a3ec6a8022cb

출처 데이터셋

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09315487B2