1,2-Dichloroethane → N-((4-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxamide

HRID 1616817Notes

Reaction equation

HRID 1616817 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([OH:13])=O)[CH:10]=1)[N:7]([CH3:14])[CH:6]=[C:5]2[CH:15]([CH3:17])[CH3:16].Cl.[NH2:19][CH2:20][C:21]1[C:22](=[O:35])[NH:23][C:24]([CH3:34])=[CH:25][C:26]=1[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>O.CS(C)=O>[CH2:27]([C:26]1[CH:25]=[C:24]([CH3:34])[NH:23][C:22](=[O:35])[C:21]=1[CH2:20][NH:19][C:11]([C:9]1[CH:10]=[C:2]([Br:1])[CH:3]=[C:4]2[C:8]=1[N:7]([CH3:14])[CH:6]=[C:5]2[CH:15]([CH3:17])[CH3:16])=[O:13])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 674669583-(aminomethyl)-4-benzyl-6-methylpyridin-2(1H)-one hydrochlorideHCID 678162465-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylic acid

Product 1

HCID 67816369N-((4-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxamideYield 89%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A 20 mL, oven dried vial was charged with 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylic acid (0.075 g, 0.253 mmol), 3-(aminomethyl)-4-benzyl-6-methylpyridin-2(1H)-one hydrochloride (0.080 g, 0.304 mmol), 1-hydroxy-7-azabenzotriazole (0.041 g, 0.304 mmol) and EDC (0.058 g, 0.304 mmol). Dimethyl sulfoxide (DMSO) (2 mL) was added via syringe, followed by N-methylmorpholine (0.111 mL, 1.013 mmol). The mixture was capped and stirred at RT over weekend. The reaction was poured into 60 mL water and the resultant mixture stirred for 10 min, then placed in a freezer for 10 min. The solids were filtered, washed with water (10 mL), air dried for 5 min, and placed in a vacuum oven (40° C.) for 2 h. Collected the solids and further dried in a vacuum oven (45° C.) for 18 h to give N-((4-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxamide (120 mg, 0.225 mmol, 89% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (s, 1H), 8.63 (t, J=4.9 Hz, 1H), 7.75 (d, J=1.8 Hz, 1H), 7.30 (m, 2H), 7.22 (m, 3H), 7.13 (s, 1H), 7.05 (d, J=1.8 Hz, 1H), 5.78 (s, 1H), 4.39 (d, J=4.8 Hz, 2H), 3.96 (s, 2H), 3.64 (s, 3H), 3.11 (dt, J=13.6, 6.8 Hz, 1H), 2.09 (s, 3H), 1.26 (m, 6H). MS (ES) [M+H]+ 506.3.

Workup

  1. customA 20 mL, oven dried vial
  2. customThe mixture was capped
  3. filtrationThe solids were filtered
  4. washwashed with water (10 mL), air
  5. customdried for 5 min
  6. waitplaced in a vacuum oven (40° C.) for 2 h
  7. customCollected the solids
  8. customfurther dried in a vacuum oven (45° C.) for 18 h

Sources & evidence

ORD record
ord-0741ccebe0cf4f499dc99034dca98ff6
Source dataset
uspto-grants-2014_07
Patent number
US08765792B2

Reaction notes

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