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 594081Notes

Reaction equation

HRID 594081 reaction equation
[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]

Participants

7

Reactant 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

Product 1

HCID 904079681-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-carboxamideYield 15%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
150 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-093ccda7c42841e9a60c93ac406176a5
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

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