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Cesium carbonate → (S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone

HRID 1051674
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HRID 1051674 반응식
Br[C:2]1[C:3]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])[C@@H:7]([CH3:17])[CH2:6][CH2:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:39]2[CH:40]=[N:41][N:42](C(OC(C)(C)C)=O)[CH:43]=2)O1.O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O>[CH:14]1([C:12]([N:8]2[C:9]3[C:4](=[C:3]([O:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:2]([C:39]4[CH:40]=[N:41][NH:42][CH:43]=4)=[CH:11][CH:10]=3)[CH2:5][CH2:6][C@@H:7]2[CH3:17])=[O:13])[CH2:15][CH2:16]1
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118086215(S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

생성물 1

HCID 118075498(S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone
수율 52%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매

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온도
100 °C

실험 절차

A 100-mL round-bottom flask was charged with (S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.400 g, 1.04 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.083 g, 0.10 mmol), cesium carbonate (0.985 g, 3.02 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.343 g, 1.17 mmol), 1,4-dioxane (10 mL) and water (3 mL). The resulting mixture stirred at 100° C. overnight and was cooled to room temperature. The reaction mixture was passed through a short pad of Celite, and the filtrate was concentrated under vacuum. The residue was purified via column chromatography on silica gel (gradient elution with 10-25% ethyl acetate/petroleum ether) to afford (S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.200 g, 52%) as a light yellow solid. MS (ESI, pos. ion) m/z 374 [M+H]+.

후처리

  1. temperaturewas cooled to room temperature
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe residue was purified via column chromatography on silica gel (gradient elution with 10-25% ethyl acetate/petroleum ether)

출처 및 근거

ORD 기록
ord-43b045220f5543deb4db07e8884da7db
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09388161B2

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