Iodopyrazine → 1'-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one

温度

80 °C

Pd2(dba)3-CHCl3 (5 mg, 0.5 mol %), 2′-(dicyclohexylphosphino)biphenyl-2-amine (8 mg, 2 mol %) and sodium tert-butoxide (13 mg, 0.14 mmol) were weighed in air and transferred into flask, followed by dioxane (750 μL), 1′-(piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4′piperidin]-2(1H)-one bis-hydrochloride (compound no. 49) (37 mg, 0.10 mmol) and iodopyrazine (viia) (20.6 mg, 0.10 mmol). The flask was flushed with nitrogen and stirred at 80° C. for 16 hours. The reaction mixture was diluted with methanol (500 μL), filtered (Whatman 0.45 μm PTFE) and subjected to reverse-phase HPLC purification (2-25% CH3CN gradient [w/0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min) to provide 1′-(1-(pyrazin-2-yl)piperidin-4-yl)spiro[benzo[d][1,3]oxazine-4,4′-piperidin]-2(1H)-one (compound no. 74). LC/MS m/z 380.2 [M+H]+, retention time 1.35 min (RP-C18, 10-99% CH3CN/0.05% TFA).

1. customtransferred into flask
2. customThe flask was flushed with nitrogen
3. additionThe reaction mixture was diluted with methanol (500 μL)
4. filtrationfiltered (Whatman 0.45 μm PTFE)
5. customsubjected to reverse-phase HPLC purification (2-25% CH3CN gradient [w/0.1% TFA (aq)] over 10 minutes, 1.0 mL injected, 35 mL/min)

ORDレコード

ord-d6bbe3c8333a4e9a90eb273ba14a97c2

出典データセット

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07696201B2