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

HRID 85515Notes

Reaction equation

HRID 85515 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:14]([OH:16])=O)[C:5]2[CH:6]=[N: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:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=1[CH2:25][CH2:26][CH3:27].ON1C2N=CC=CC=2N=N1.CN1CCOCC1.C(Cl)CCl.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([C:14]([NH:17][CH2:18][C:19]2[C:20](=[O:29])[NH:21][C:22]([CH3:28])=[CH:23][C:24]=2[CH2:25][CH2:26][CH3:27])=[O:16])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 11430Potassium CarbonateHCID 181649HOAtHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674654436-Bromo-1-isopropyl-1H-indazole-4-carboxylic acid

Product 1

HCID 674653266-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamideYield 75.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6-Bromo-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (80 mg, 0.28 mmol), 3-(aminomethyl)-6-methyl-4-propyl-2(1H)-pyridinone (112 mg, 0.38 mmol) and 1-hydroxy-7-azabenzotriazole (57.7 mg, 0.42 mmol) were stirred in 3 mL of DMSO for 10 min under nitrogen. N-Methylmorpholine (0.12 ml, 1.13 mmol) was added along with EDC (81 mg, 0.42 mmol) and the mixture was stirred at room temperature overnight under nitrogen. Ice-water was added and solids crashed out. Then 10% K2CO3 was added to adjust the pH to about 8-9. Then the reaction was stirred at room temperature for 10 min and let stand for 10 min. Solids were filtered off, dissolved in DMF and water was added. Solids that precipitated out were filtered off, air-dried for 15 min and dried in vacuum oven for 2 h to give the title compound (94 mg, 73%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.62 (t, J=4.93 Hz, 1H) 8.37 (s, 1H) 8.20 (s, 1H) 7.69 (d, J=1.26 Hz, 1H) 5.91 (s, 1H) 5.06 (dt, J=13.14, 6.57 Hz, 1H) 4.36 (d, J=4.80 Hz, 2H) 2.14 (s, 3H) 1.48-1.56 (m, 2H) 1.47 (s, 3H) 1.45 (s, 3H) 0.89 (t, J=7.33 Hz, 3H); MS(ES) [M+H]+ 445.1, 446.9.

Workup

  1. stirringThen the reaction was stirred at room temperature for 10 min
  2. waitlet stand for 10 min
  3. filtrationSolids were filtered off
  4. dissolutiondissolved in DMF
  5. additionwater was added
  6. customSolids that precipitated out
  7. filtrationwere filtered off
  8. customair-dried for 15 min
  9. customdried in vacuum oven for 2 h

Sources & evidence

ORD record
ord-2dc62a92e7854fc5adb9c4c8bb592d07
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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