Cesium carbonate → (R)-2-(5-cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)butanamide

HRID 84909

反応式

HRID 84909 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([NH2:12])=[O:11])[C:5]([F:15])=[CH:4][C:3]=1[C:16]#[N:17].[NH2:18][C:19]1[CH:20]=[N:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:16]([C:3]1[CH:4]=[C:5]([F:15])[C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([NH2:12])=[O:11])=[N:7][C:2]=1[NH:18][C:19]1[CH:20]=[N:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2)#[N:17]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 113753-AminoquinolineHCID 634876Binap, (A+-)-HCID 86666160(R)-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)butanamide

生成物 1

HCID 67508532(R)-2-(5-cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)butanamide

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

The mixture of (R)-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)butanamide (120 mg, 0.46 mmol), 3-aminoquinoline (150 mg, 1.0 mmol), Pd(OAc)2 (22 mg, 0.11 mmol), racemic BINAP (68 mg, 0.11 mmol) and fine-powder cesium carbonate (0.50 g, 1.65 mmol) in 20 mL dioxane was degassed using argon stream for 3 min. It was then stirred at 100° C. in argon atmosphere for overnight. The mixture was cooled to RT, concentrated in vacuo, taken into 200 mL EtOAc and 50 mL water. The organic phase was separated and washed with brine. It was dried, concentrated and purified using silica flash column (35% EtOAc in DCM) to give (R)-2-(5-cyano-3-fluoro-6-(quinolin-3-ylamino)pyridin-2-ylamino)butanamide. It was dissolved in 4 mL DMSO. To it were added 2 mL 50% H2O2 and then powder potassium carbonate (91 mg, 0.66 mmol). The mixture was stirred at RT for 30 min. It was diluted with 4 mL 1N HCl. The mixture was subjected to reverse prep HPLC to isolate the title compound as HCl salt (102 mg).

後処理

  1. customwas degassed
  2. customfor 3 min
  3. temperatureThe mixture was cooled to RT
  4. concentrationconcentrated in vacuo
  5. customThe organic phase was separated
  6. washwashed with brine
  7. customIt was dried
  8. concentrationconcentrated
  9. custompurified

出典と根拠

ORDレコード
ord-7347f16626df4c42bafffffab8e9383f
出典データセット
uspto-grants-2014_09
特許番号
US08846928B2

関連ノート

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