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Dimethylformamide → Methyl 6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinate

HRID 2080273
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HRID 2080273 반응식
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[N:3]=1.[Cl-].[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O)#[N:24].C([O-])([O-])=O.[K+].[K+].[CH3:40][N:41]([CH:43]=O)C>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]>[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:3][CH2:2][C:11]2[CH:40]=[N:41][CH:43]=[CH:5][CH:10]=2)=[O:8])=[C:4]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[N:3]=1)#[N:24].[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[N:3]=1)#[N:24]
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참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27346102-Cyanophenylboronic acidHCID 86626130Chloride methyl 6-chloro-2-(3-fluorophenethylamino)nicotinate

생성물 2

HCID 57542380Methyl 6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinate수율 82%
HCID 57542525
6-(2-cyanophenyl)-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide

시약·촉매·용매 1

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매

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온도
100 °C

실험 절차

A mixture of chloride methyl 6-chloro-2-(3-fluorophenethylamino)nicotinate (30.8 g, 0.1 mol), 2-cyanophenyl boronic acid (17.6 g, 0.12 mol), PdCl2(dppf)2 (3.6 g, 5.0 mmol), K2CO3 (41.4 g, 0.3 mol) and anhydrous DMF (100 mL) was degassed with nitrogen for 30 min. The mixture was then stirred at 100° C. for 2 hrs. The mixture was filtered through the Celite and washed with EtOAc. The filtrate was diluted with EtOAc, washed with brine and concentrated to dryness. The residue was purified by silica gel flash chromatography using hexane-EtOAc (4:1) as eluant to give the desired product methyl 6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinate as a yellow solid (31 g, 82%). LRMS (M+H+) m/z 376.1.

후처리

  1. customwas degassed with nitrogen for 30 min
  2. filtrationThe mixture was filtered through the Celite
  3. washwashed with EtOAc
  4. additionThe filtrate was diluted with EtOAc
  5. washwashed with brine
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by silica gel flash chromatography

출처 및 근거

ORD 기록
ord-f5e187d44544445d97e35997c9398d3e
출처 데이터셋
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07932270B2

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