Cyclopropanesulfinic acid → 1-cyclopentyl-6-(cyclopropylsulfonyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide

HRID 85506Notes

Reaction equation

HRID 85506 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[CH:29]1([S:32]([OH:34])=[O:33])[CH2:31][CH2:30]1.CNCCNC.CNCCNC>FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O.CS(C)=O>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([S:32]([CH:29]4[CH2:31][CH2:30]4)(=[O:34])=[O:33])[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

6

Reactant 3

HCID 14563239Cyclopropanesulfinic acidHCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamideHCID 86677389N,N'-dimethyl-1,2-ethanediamine methyl[2-(methylamino)ethyl]amine

Product 1

HCID 545964951-cyclopentyl-6-(cyclopropylsulfonyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamideYield 60.8%

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a 10-mL microwave tube were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (70 mg, 0.158 mmol), cyclopropanesulfinic acid (40.8 mg, 0.316 mmol), dimethyl sulfoxide (3 mL), N,N′-dimethyl-1,2-ethanediamine methyl[2-(methylamino)ethyl]amine (55.7 mg, 0.632 mmol), and copper(II) trifluoromethanesulfonate (57.1 mg, 0.158 mmol), and the mixture was degassed for 5 min by bubbling nitrogen. The tube was sealed and the mixture irradiated at 120° C. (microwave) for 3 h. The mixture was filtered and the DMSO solution was purified using reverse-phase HPLC to give 45 mg of product. The product was collected as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00-1.12 (m, 2H), 1.15-1.31 (m, 2H), 1.67-1.79 (m, 2H), 1.84-1.94 (m, 2H), 1.96-2.08 (m, 2H), 2.12-2.28 (m, 8H), 2.93-3.05 (m, 1H), 4.38 (d, J=5.05 Hz, 2H), 5.43 (quin, J=7.01 Hz, 1H), 5.90 (s, 1H), 8.01 (d, J=1.26 Hz, 1H), 8.44 (s, 1H), 8.52 (s, 1H), 8.83 (t, J=4.93 Hz, 1H), 11.57 (s, 1H); LCMS: (M+H)+=469.0

Workup

  1. customthe mixture was degassed for 5 min
  2. customby bubbling nitrogen
  3. customThe tube was sealed
  4. customthe mixture irradiated at 120° C. (microwave) for 3 h
  5. filtrationThe mixture was filtered
  6. customthe DMSO solution was purified

Sources & evidence

ORD record
ord-c180161f20e5475fa14d830d1dce1173
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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