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 540364노트

반응식

HRID 540364 반응식
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

참가 물질

8

반응물 4

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

생성물 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)-methanone수율 53%

시약·촉매·용매 3

HCID 634876Binap, (A+-)-촉매HCID 887Methanol용매2회HCID 6344Dichloromethane용매2회

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온도
85 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-955dc7649db44440a19caa49659f92ac
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871788B2

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