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

HRID 1476984Notes

Reaction equation

HRID 1476984 reaction equation
[CH3:1][CH:2]([N:4]1[C:12]2[C:11]([O:13][CH3:14])=[CH:10][CH:9]=[C:8]([C:15]([OH:17])=O)[C:7]=2[CH:6]=[CH:5]1)[CH3:3].[NH2:18][CH2:19][C:20]1[C:21](=[O:30])[NH:22][C:23]([CH3:29])=[CH:24][C:25]=1[CH2:26][CH2:27][CH3:28].ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>O.CS(C)=O>[CH3:3][CH:2]([N:4]1[C:12]2[C:11]([O:13][CH3:14])=[CH:10][CH:9]=[C:8]([C:15]([NH:18][CH2:19][C:20]3[C:21](=[O:30])[NH:22][C:23]([CH3:29])=[CH:24][C:25]=3[CH2:26][CH2:27][CH3:28])=[O:17])[C:7]=2[CH:6]=[CH:5]1)[CH3:1]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674686821-(1-Methylethyl)-7-(methyloxy)-1H-indole-4-carboxylic acid

Product 1

HCID 674679531-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-7-(methyloxy)-1H-indole-4-carboxamideYield 60.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Added 1-(1-methylethyl)-7-(methyloxy)-1H-indole-4-carboxylic acid (160 mg, 0.686 mmol), 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (186 mg, 0.857 mmol), 1-hydroxy-7-azabenzotriazole (187 mg, 1.372 mmol), EDC (263 mg, 1.372 mmol) and N-methylmorpholine (0.302 mL, 2.74 mmol) to DMSO (10 mL) and stirred mixture at RT for 16 h. Added 25 ml of water and stirred for 10 minutes. Filtered off solids and dried in vacuo. The solids were purified by column chromatography (Biotage; 0% to 15% gradient MeOH:DCM; 10 g-HP-silica gel column) to give 165 mg of 1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-7-(methyloxy)-1H-indole-4-carboxamide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.01 (t, 3H), 1.45 (d, J=6.57 Hz, 6H), 1.63 (m, J=7.45, 7.45, 7.45, 7.45, 7.33 Hz, 2H), 2.24 (s, 3H), 2.74 (t, J=7.58 Hz, 2H), 3.96 (s, 3H), 4.64 (br. s., 2H), 5.45 (quin, J=6.63 Hz, 1H), 5.97 (s, 1H), 6.62 (d, J=8.08 Hz, 1H), 6.94 (d, J=3.28 Hz, 1H), 7.24 (d, J=3.28 Hz, 1H), 7.53 (d, J=8.08 Hz, 1H), 7.74 (br. s., 1H), 12.46 (br. s., 1H). MS(ES) [M+H]+ 395.7.

Workup

  1. stirringstirred for 10 minutes
  2. filtrationFiltered off solids
  3. customdried in vacuo
  4. customThe solids were purified by column chromatography (Biotage; 0% to 15% gradient MeOH:DCM; 10 g-HP-silica gel column)

Sources & evidence

ORD record
ord-4ffe63802cb2452da3025aa88109f4a9
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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