Potassium Carbonate → 1-methyl-4-(5-nitro-2-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-1,4-dihydro-5H-tetrazol-5-one

HRID 633406Notes

Reaction equation

HRID 633406 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH3:17])[N:13]=[N:12]1.[O:18]1[CH2:21][CH:20]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:19]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH3:17][N:14]1[C:15](=[O:16])[N:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[N:25]2[CH2:26][CH2:27][N:22]([CH:20]3[CH2:21][O:18][CH2:19]3)[CH2:23][CH2:24]2)[N:12]=[N:13]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574162871-(Oxetan-3-yl)piperazineHCID 582871741-(2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

Product 1

HCID 867045031-methyl-4-(5-nitro-2-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-1,4-dihydro-5H-tetrazol-5-oneYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-(2-fluoro-5-nitrophenyl)-4-methyl-1,4-dihydro-5H-tetrazol-5-one (1.1 g, 1.0 eq, 4.5 mmol) (see, e.g., WO 2011/068898), 1-(oxetan-3-yl)piperazine (0.64 g, 1.0 eq, 4.5 mmol) was dissolved in annhydrous DMF (100 mL) and stirred at room temperature. K2CO3 (1.9 g, 3.0 eq, 13.5 mmol) was added to the above solution and the heterogeneous mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc (50 mL) and partitioned with H2O (50 mL). The layers were separated and the aqueous layer was washed with EtOAc (50 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to leave a crude solid. Purification of the crude solid by column chromatography on silica gel (ISCO System) using 20% MeOH in CH2Cl2/CH2Cl2 (gradient system from 1:9 to 1:1) as eluent gave the product in 50% yield.

Workup

  1. stirringthe heterogeneous mixture was stirred at room temperature overnight
  2. custompartitioned with H2O (50 mL)
  3. customThe layers were separated
  4. washthe aqueous layer was washed with EtOAc (50 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto leave a crude solid
  8. customPurification of the crude solid by column chromatography on silica gel (ISCO System)
  9. customgave the product in 50% yield

Sources & evidence

ORD record
ord-b2abd5d0f8894acc84e700c8892e8f40
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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