Cesium carbonate → 1-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile

HRID 1192600ノート

反応式

HRID 1192600 の反応式
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[NH:24]1[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:8]1[C:7]([N:24]2[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]2)=[C:16]2[C:11]([CH:12]=[CH:13][CH:14]=[N:15]2)=[C:10]([Cl:17])[CH:9]=1)(=[O:20])[CH3:19]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 42614784Pyrrolidine-3-carbonitrile hydrochlorideHCID 58368658HCID 58368658、化合物

生成物 1

HCID 583686301-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile収率 16%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), pyrrolidine-3-carbonitrile hydrochloride (0.054 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and evaporated to dryness. The resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give the desired product (16 mg, 16%). LCMS calculated for C16H15ClN3O (M+H)+: m/z=300.1; Found: 300.0.

後処理

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane)

出典と根拠

ORDレコード
ord-aaaf1407e22e4f7fb92131cc7fd2c91b
出典データセット
uspto-grants-2014_03
特許番号
US08680108B2

反応ノート

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