Sodium Hydroxide → 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

HRID 1501686Notes

Reaction equation

HRID 1501686 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:18]([O:20]C)=O)[C:7]2[CH:8]=[N:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[CH:12]=1.[NH2:22][CH2:23][C:24]1[C:25](=[O:32])[NH:26][C:27]([CH3:31])=[CH:28][C:29]=1[CH3:30].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CCO.CS(C)=O>[Br:3][C:4]1[CH:5]=[C:6]([C:18]([NH:22][CH2:23][C:24]2[C:25](=[O:32])[NH:26][C:27]([CH3:31])=[CH:28][C:29]=2[CH3:30])=[O:20])[C:7]2[CH:8]=[N:9][N:10]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17]3)[C:11]=2[CH:12]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 67468180Methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

Product 1

HCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamideYield 56.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Aqueous NaOH (0.68 g, 17.18 mmol) was added to a solution of methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate (3.7 g, 11.45 mmol) in EtOH (40 mL) and stirred at 60° C. for 1 h. After completion of the reaction, ethanol was removed under reduced pressure and the residue acidified using 1N HCl solution. The resulting precipitate was filtered and dried under vacuum. This crude acid (3.2 g, 10.3 mmol) was then dissolved in DMSO (20 mL) and 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (3.15 g, 20.77 mmol) added to it. The reaction mixture was stirred at room temperature for 15 min before PYBOP (8.1 g, 15.5 mmol) was added and left to stir overnight. After completion of the reaction, reaction mass was poured into ice to obtain solid which was filtered and washed with acetonitrile then ether to provide the desired 6-bromo-1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide (2.6 g, 56.5%). LCMS: 443.05 (M+1)+; HPLC: 95.00% (@ 254 nm) (Rt; 7.195); 1H NMR (DMSO-d6, 400 MHz) δ 11.52 (s, 1H), 8.61 (t, 1H, J=4.8 Hz), 8.36 (s, 1H), 8.19 (s, 1H), 7.70 (s, 1H), 5.88 (s, 1H), 5.23-5.20 (m, 1H), 4.33 (d, 2H, J=4.8 Hz), 2.20 (s, 3H), 2.12 (s, 3H), 1.98 (m, 2H), 1.97-1.90 (m, 2H), 1.87-1.86 (m, 2H), 1.73-1.67 (m, 2H).

Workup

  1. customwas removed under reduced pressure
  2. filtrationThe resulting precipitate was filtered
  3. customdried under vacuum
  4. additionwas added
  5. waitleft
  6. stirringto stir overnight
  7. customAfter completion of the reaction, reaction mass
  8. additionwas poured into ice
  9. customto obtain solid which
  10. filtrationwas filtered
  11. washwashed with acetonitrile

Sources & evidence

ORD record
ord-6bea186d7fda431fbcdcf7ccaef18e06
Source dataset
uspto-grants-2015_12
Patent number
US09206157B2

Reaction notes

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