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1,4-Dioxane → 2-(4-cyclopropylpyridin-3-yl)-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1844036
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HRID 1844036 반응식
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][C:10]2=[O:13])=[CH:5][CH:4]=1.[CH:16]1([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][C:20]=2I)[CH2:18][CH2:17]1.O1CCOCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)(Cl)Cl.[Cu](I)I.CO>[CH:16]1([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][C:20]=2[N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:3]([C:2]([F:1])([F:14])[F:15])=[CH:4][CH:5]=3)[C:10]2=[O:13])[CH2:18][CH2:17]1
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참가 물질

8

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 668015937-(Trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-oneHCID 668018874-Cyclopropyl-3-iodopyridine

생성물 1

HCID 569430552-(4-cyclopropylpyridin-3-yl)-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one수율 12.9%

시약·촉매·용매 3

HCID 83717
Copper iodide
촉매
HCID 887Methanol용매
HCID 6212Chloroform용매

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온도
120 °C

실험 절차

7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one (I-4-d: 100 mg, 0.465 mmol) was reacted with 4-cyclopropyl-3-iodopyridine (I-73c: 125.3 mg, 0.51 mmol), 1,4-dioxane (5 mL), copper iodide (8.8 mg, 0.0465 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (6.6 mg, 0.0465 mmol) and potassium phosphate (246 mg, 1.16 mmol). The resulting mixture was stirred for 24 hours at 120° C. The reaction was monitored by TLC (10% methanol in CHCl3). The reaction mixture was concentrated to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3), followed by preparative HPLC afforded 20 mg of the product (12.9% yield).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. customto afford the crude product
  3. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

출처 및 근거

ORD 기록
ord-fb71b6cd3f614efd9c5ebf1f070b470d
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08946260B2

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