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Dichloromethane → 1-ethyl-N-(4-methyl-3-(1-methyl-5-morpholino-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-6-oxo-5-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide

HRID 594081
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HRID 594081 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:22])=[C:6]([C:8]2[CH:9]=[C:10]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.Br[C:24]1[CH:25]=[C:26]([C:33]([F:36])([F:35])[F:34])[C:27](=[O:32])[N:28]([CH2:30][CH3:31])[CH:29]=1.C(Cl)Cl.C1CCN2C(=NCCC2)CC1.C1C[O:54][CH2:53]C1>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]>[CH2:30]([N:28]1[C:27](=[O:32])[C:26]([C:33]([F:36])([F:35])[F:34])=[CH:25][C:24]([C:53]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH3:22])=[C:6]([C:8]3[CH:9]=[C:10]([N:16]4[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=3)[CH:7]=2)=[O:54])=[CH:29]1)[CH3:31]
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참가 물질

7

반응물 5

HCID 6344DichloromethaneHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 904081725-(5-amino-2-methylphenyl)-1-methyl-3-morpholinopyridin-2(1H)-oneHCID 904088165-bromo-1-ethyl-3-(trifluoromethyl)pyridin-2(1H)-one

생성물 1

HCID 90407968
1-ethyl-N-(4-methyl-3-(1-methyl-5-morpholino-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-6-oxo-5-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide
수율 15%

시약·촉매·용매 1

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

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온도
150 °C

실험 절차

In a microwave tube was added 5-(5-amino-2-methylphenyl)-1-methyl-3-morpholinopyridin-2(1H)-one (1.0 equiv.), 5-bromo-1-ethyl-3-(trifluoromethyl)pyridin-2(1H)-one (2.0 equiv.), PdCl2(dppf).CH2Cl2 adduct (0.1 equiv.), Mo(CO)6 (1.0 equiv.), and THF (0.3 M). The mixture was capped and stirred while DBU (3.0 equiv.) was added, fizzing occurred and the tube was subsequently heated in the microwave at 150° C. for 15 min at which time LCMS indicated full conversion to product (M+H=517). The reaction was filtered, concentrated, and purified via preparative HPLC to yield 1-ethyl-N-(4-methyl-3-(1-methyl-5-morpholino-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-6-oxo-5-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide (15% yield). 1H NMR (400 MHz, <cd3od>) δ ppm 1.42 (t, J=7.24 Hz, 3H) 2.30 (s, 3H) 3.08-3.21 (m, 4H) 3.64 (s, 3H) 3.80-3.92 (m, 4H) 4.16 (q, J=7.04 Hz, 2H) 6.93 (d, J=1.96 Hz, 1H) 7.28 (d, J=8.22 Hz, 1H) 7.34 (d, J=1.96 Hz, 1H) 7.47-7.60 (m, 2H) 8.48 (d, J=1.96 Hz, 1H) 8.70 (d, J=2.35 Hz, 1H). LCMS (m/z) (M+H)=517.1, Rt=0.81 min.

후처리

  1. customThe mixture was capped
  2. additionwas added
  3. filtrationThe reaction was filtered
  4. concentrationconcentrated
  5. custompurified via preparative HPLC

출처 및 근거

ORD 기록
ord-093ccda7c42841e9a60c93ac406176a5
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09242969B2

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