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

HRID 873351Notes

Reaction equation

HRID 873351 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:14]([OH:16])=O)[C:5]2[CH:6]=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=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>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([C:14]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[CH:6]=[CH:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 674686386-bromo-1-(1-methylethyl)-1H-indole-4-carboxylic acid

Product 1

HCID 546701646-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indole-4-carboxamideYield 74.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylic acid (0.71 g, 2.52 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone (0.575 g, 3.77 mmol), 1-hydroxy-7-azabenzotriazole (0.514 g, 3.77 mmol), and EDC (0.724 g, 3.77 mmol) in dimethylsulfoxide (20 mL) was added quickly N-methylmorpholine (1.107 mL, 10.07 mmol) via syringe. The solids slowly dissolved and the reaction was maintained at RT overnight. The reaction was slowly poured into ice-water (300 mL), stirred for 10 min, then allowed to sit for 10 min. The solids were filtered and washed with water (100 mL), airdried for 15 min, then dried in vacuum oven at 45° C. for 4 h to give 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indole-4-carboxamide (0.82 g, 1.871 mmol, 74.4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.46 (m, 6 H) 2.09-2.15 (m, 3 H) 2.21 (s, 3 H) 4.32 (d, J=5.05 Hz, 2 H) 4.82 (quin, J=6.63 Hz, 1 H) 5.88 (s, 1 H) 6.86 (d, J=3.28 Hz, 1 H) 7.51 (d, J=1.77 Hz, 1 H) 7.62 (d, J=3.28 Hz, 1 H) 7.92 (s, 1 H) 8.31 (t, J=4.93 Hz, 1 H) 11.55 (br. s., 1 H). MS (ES) [M+H]+416.0.

Workup

  1. dissolutionThe solids slowly dissolved
  2. waitto sit for 10 min
  3. filtrationThe solids were filtered
  4. washwashed with water (100 mL)
  5. waitairdried for 15 min
  6. customdried in vacuum oven at 45° C. for 4 h

Sources & evidence

ORD record
ord-218850311d0c4dcb9a79886313e4bef5
Source dataset
uspto-grants-2015_03
Patent number
US08975291B2

Reaction notes

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