Triphenylphosphine → 5-Cyclopropyl-2-(5-methylpyridin-2-yl)-6-nitro-2H-indazole

HRID 63532Notes

Reaction equation

HRID 63532 reaction equation
[CH:1]1([C:4]2[C:5]([N+:15]([O-:17])=[O:16])=[CH:6][C:7]([N+:12]([O-])=O)=[C:8]([CH:11]=2)[CH:9]=O)[CH2:3][CH2:2]1.ClC1C=CC([N:25]2[C:33](C(NC)=O)=[C:32]3[C:27](C=[C:29]([NH:41]S(C)(=O)=O)[C:30](C4CC4)=[CH:31]3)=N2)=CC=1.CC1C=CC(N)=NC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CCO.C(Cl)Cl>[CH:1]1([C:4]2[C:5]([N+:15]([O-:17])=[O:16])=[CH:6][C:7]3[C:8](=[CH:9][N:41]([C:29]4[CH:30]=[CH:31][C:32]([CH3:27])=[CH:33][N:25]=4)[N:12]=3)[CH:11]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 153482-Amino-5-methylpyridineHCID 569631692-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamideHCID 866664205-Cyclopropyl-2,4-dinitrobenzaldehyde

Product 1

HCID 866989485-Cyclopropyl-2-(5-methylpyridin-2-yl)-6-nitro-2H-indazoleYield 43%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-cyclopropyl-2,4-dinitrobenzaldehyde (prepared according to the synthesis of Compound (1)) (50 mg, 0.212 mmol) in EtOH (750 mL) was added 5-methylpyridin-2-amine (25 mg, 0.23 mmol) and the resultant solution stirred at RT for 2d after which time a solid had precipitated from solution. Triphenylphosphine (167 mg, 0.64 mmol) was added in a single portion and the reaction then heated at 100° C. in a sealed tube for 4 h. Upon cooling to RT, the reaction was diluted with DCM (2 mL) and the organics were washed with aq. 30% hydrogen peroxide solution (2 mL). The organics were separated and filtered through a plug of MgSO4 and then purified by automated column chromatography (Biotage SP4, Grace 4 g silica cartridge) eluting with EtOAc:n-heptane (gradient elution, 0% equil. (2 CV), 0% (1CV), 0 to 100% (35 CV), 100% (5 CV)) to give (ii) (27 mg, 43%). ESI-MS: calculated [M+H]+ 295.1. observed [M+H]+ 295.2.

Workup

  1. customhad precipitated from solution
  2. customthe reaction
  3. temperatureUpon cooling to RT
  4. washthe organics were washed with aq. 30% hydrogen peroxide solution (2 mL)
  5. customThe organics were separated
  6. filtrationfiltered through a plug of MgSO4
  7. custompurified by automated column chromatography (Biotage SP4, Grace 4 g silica cartridge)
  8. washeluting with EtOAc

Sources & evidence

ORD record
ord-5f4f4a3d5dc140459a81848796a366ec
Source dataset
uspto-grants-2016_09
Patent number
US09447080B2

Reaction notes

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