Cesium carbonate → 5-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-one

HRID 2069728ノート

反応式

HRID 2069728 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:12][N:11]([CH3:13])[CH2:10]2)=[CH:4][N:3]=1.[NH2:14][C:15]1[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=[C:19]([Br:21])[CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.O>[Br:21][C:19]1[CH:20]=[C:15]([NH:14][C:2]2[CH:7]=[CH:6][C:5]([O:8][CH:9]3[CH2:12][N:11]([CH3:13])[CH2:10]3)=[CH:4][N:3]=2)[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 529112683-Amino-5-bromo-1-methyl-1,2-dihydropyridin-2-oneHCID 594737702-Bromo-5-[(1-methyl-3-azetidinyl)oxy]pyridine2 回

生成物 1

HCID 580442285-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-one収率 41.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 2-Bromo-5-(1-methyl-azetidin-3-yloxy)-pyridine (0.327 g, 1.32 mmol) and 3-Amino-5-bromo-1-methyl-1H-pyridin-2-one (0.321 g, 1.58 mmol) in dioxane (5.5 mL) add Cs2CO3 (0.645 g, 1.98 mmol), xantphos (0.153 g, 0.264 mmol) and bubbled argon through reaction mixture for 15 min. Add Pd (OAc)2 (0.03 g, 0.132 mmol) in the end. The reaction was heated at 100° C. under argon for 3 h. TLC shows 2-Bromo-5-(1-methyl-azetidin-3-yloxy)-pyridine was gone. The reaction mixture was treated with water (30 mL) and extracted with dichloromethane (3×20 mL). Organic phase was concentrated and loaded onto silica gel column separation. Using 3-5% MeOH in DCM gave 5-bromo-1-methyl-3-[5-(1-methyl-azetidin-3-yloxy)-pyridin-2-ylamino]-1H-pyridin-2-one as green solid (200 mg, 40% yield).

後処理

  1. custombubbled argon
  2. customthrough reaction mixture for 15 min
  3. extractionextracted with dichloromethane (3×20 mL)
  4. concentrationOrganic phase was concentrated and loaded onto silica gel column separation

出典と根拠

ORDレコード
ord-e7ca2f13f9b841369868c214c49900e0
出典データセット
uspto-grants-2012_10
特許番号
US08299077B2

反応ノート

読み込み中…