Toluene → [7-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-(tetrahydro-pyran-4-yl)-methanone

HRID 540364ノート

反応式

HRID 540364 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:20][C@H:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C@H:26]1[CH2:30][CH2:29][NH:28][CH2:27]1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>CO.C(Cl)Cl.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>[CH3:20][C@H:21]1[CH2:25][CH2:24][CH2:23][N:22]1[C@H:26]1[CH2:30][CH2:29][N:28]([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:12]([CH:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[CH2:9]3)=[CH:4][CH:3]=2)[CH2:27]1

参加物

8

反応物 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinylHCID 67466031HCID 67466031、化合物

生成物 1

HCID 54596984[7-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-(tetrahydro-pyran-4-yl)-methanone収率 53%

試薬・触媒・溶媒 3

HCID 634876Binap, (A+-)-触媒HCID 887Methanol溶媒2 回HCID 6344Dichloromethane溶媒2 回

反応条件

温度
85 °C

実験手順

A vial was charged with (7-bromo-3,4-dihydro-1H-isoquinolin-2-yl)-(tetrahydro-pyran-4-yl)-methanone (162 mg, 0.5 mmol), (2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl (90 mg, 0.55 mmol), and sodium tert-butoxide (69 mg, 0.7 mmol), tris(dibenzylideneacetone)dipalladium-(0) (4.6 mg, 0.005 mmol), BINAP (9.3 mg, 0.015 mmol), and toluene (4 mL) under argon. The vial was capped with a septum and was heated to 85° C. (external) with stirring until the starting material was completely consumed as monitored by TLC analysis. The mixture was allowed to cool to room temperature, taken up in ether (5.0 mL), filtered, and concentrated. The crude product was then purified further by flash chromatography on silica gel, eluted with 3% MeOH in DCM and 7.5% MeOH in DCM to 105 mg (53% yield) of the title compound as a tan solid.

後処理

  1. customThe vial was capped with a septum
  2. customwas completely consumed
  3. temperatureto cool to room temperature
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was then purified further by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-955dc7649db44440a19caa49659f92ac
出典データセット
uspto-grants-2014_10
特許番号
US08871788B2

反応ノート

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