Cesium carbonate → 4-Chloro-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde

HRID 1022028ノート

反応式

HRID 1022028 の反応式
[C:1]1(=[O:13])[C:5]2[CH:6]=[C:7]3[N:12]([C:4]=2[CH2:3][NH:2]1)[CH2:11][CH2:10][CH2:9][CH2:8]3.Br[C:15]1[N:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:16]=1[CH:17]=[O:18].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.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:23][C:19]1[C:16]([CH:17]=[O:18])=[C:15]([N:2]2[CH2:3][C:4]3[N:12]4[C:7]([CH2:8][CH2:9][CH2:10][CH2:11]4)=[CH:6][C:5]=3[C:1]2=[O:13])[N:22]=[CH:21][CH:20]=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 866839142-Bromo-4-chloropyridine-3-carbaldehydeHCID 866844512,3,5,6,7,8-Hexahydro-1H-pyrrolo[3,4-b]indolizin-1-one

生成物 1

HCID 866844524-Chloro-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde収率 42%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 238d (400 mg, 2.27 mmol), 2-bromo-4-chloronicotinaldehyde (1.50 g, 6.90 mmol, 3.0 eq.), Pd2(dba)3 (208 mg, 0.227 mmol, 0.1 eq.), xantphos (131 mg, 0.227 mmol, 0.1 eq.), Cs2CO3 (1.50 g, 4.54 mmol, 2.0 eq.), and dioxane (30 mL). After bubbling nitrogen through the resulting mixture for 30 minutes, the reaction mixture was stirred at 90° C. for 16 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residual was purified by silica-gel column chromatography eluting with 1:3 ethyl acetate/petroleum ether to afford 238e (300 mg, 42%) as a light yellow solid. MS-ESI: [M+H]+ 316.1.

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  3. temperaturethe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residual was purified by silica-gel column chromatography
  7. washeluting with 1:3 ethyl acetate/petroleum ether

出典と根拠

ORDレコード
ord-01cde6e342fc49ef92b5e150b38fd652
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

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