1,2-Dichloroethane → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-7-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide

HRID 1476980Notes

Reaction equation

HRID 1476980 reaction equation
[CH3:1][C:2]1[C:10]2[N:9]([CH:11]([CH3:13])[CH3:12])[CH:8]=[CH:7][C:6]=2[C:5]([C:14]([OH:16])=O)=[CH:4][CH:3]=1.[NH2:17][CH2:18][C:19]1[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=1[CH3:25].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>O.CS(C)=O>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:14]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([CH:11]([CH3:12])[CH3:13])[C:10]=2[C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:16]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 674672047-Methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid

Product 1

HCID 67468469N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-7-methyl-1-(1-methylethyl)-1H-indole-4-carboxamideYield 65.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Added 7-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid (52 mg, 0.239 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone (56.4 mg, 0.299 mmol), 1-hydroxy-7-azabenzotriazole (65.2 mg, 0.479 mmol), EDC (92 mg, 0.479 mmol) and N-methylmorpholine (0.105 mL, 0.957 mmol) to Dimethyl Sulfoxide (DMSO) (10 mL) and stirred at RT for 16 h. Added 25 ml of water and let stir for 10 minutes. Filtered off solids. Dissolved solids in DCM, washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (Biotage; 0% to 20% gradient MeOH:DCM; 10 g-HP-silica gel column) to give 55 mg of N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-7-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.49 (d, 6H), 2.24 (s, 3H), 2.44 (s, 3H), 2.75 (s, 3H), 4.63 (d, J=4.55 Hz, 2H), 5.17 (dt, J=13.20, 6.66 Hz, 1H), 5.97 (s, 1H), 6.91 (d, J=7.58 Hz, 1H), 7.01 (d, J=3.54 Hz, 1H), 7.29 (d, J=3.28 Hz, 1H), 7.39 (d, J=7.33 Hz, 1H), 7.69 (br. s., 1H), 12.59 (br. s., 1H). MS(ES) [M+H]+ 352.4.

Workup

  1. stirringlet stir for 10 minutes
  2. filtrationFiltered off solids
  3. dissolutionDissolved solids in DCM
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (Biotage; 0% to 20% gradient MeOH:DCM; 10 g-HP-silica gel column)

Sources & evidence

ORD record
ord-69f227a148004606a8c89c708b48085a
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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