1H-1,2,4-Triazole → HCID 57461992, compound

HRID 1868129Notes

Reaction equation

HRID 1868129 reaction equation
F[C:2]1[CH:3]=[C:4]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][C:18]=3[C:25]([F:28])([F:27])[F:26])[CH2:13][C@H:12]2[CH3:29])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[NH:30]1[CH:34]=[N:33][CH:32]=[N:31]1.C([O-])([O-])=O.[K+].[K+].CN1C(=O)CCC1>ClCCl.[Cu]I>[CH3:29][C@H:12]1[N:11]([S:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([N:30]3[CH:34]=[N:33][CH:32]=[N:31]3)[CH:3]=2)(=[O:10])=[O:9])[CH2:16][CH2:15][N:14]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][C:18]=2[C:25]([F:27])([F:28])[F:26])[CH2:13]1

Participants

7

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 57418343HCID 57418343, compound

Product 1

HCID 57461992HCID 57461992, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
166 °C

Procedure

A mixture of 4-{(3R)-4-[(3-fluorophenyl)sulfonyl]-3-methylpiperazin-1-yl}-3-(trifluoromethyl)benzonitrile (349 mg, 0.82 mmol), 1,2,4-triazole (112.6 mg, 1.64 mmol), K2CO3 (226.7 mg, 1.64 mmol), and CuI (15.6 mg, 0.082 mmol) were charged to a microwave vial. NMP (3 mL) was introduced under nitrogen atmosphere and the reaction mixture was heated at 166° C. for 3 hr in an oil bath. Reaction was complete as determined by TLC. Reaction mixtures was diluted with dichloromethane, washed with water, saturated brine then dried over Na2SO4 and concentrated. The crude product was purified via prep HPLC under neutral condition to yield 4-((3R)-3-methyl-4-{[3-(1H-1,2,4-triazol-1-yl)phenyl]sulfonyl}piperazin-1-yl)-3-(trifluoromethyl)benzonitrile as a light tan color solid (176.8 mg, 45.3% yield). HRMS: calcd for C21H19F3N6O2S+H+, 477.13150. found (ESI-FTMS, [M+H]1+), 477.13303.

Workup

  1. additionwere charged to a microwave vial
  2. customReaction
  3. customReaction mixtures
  4. washwashed with water, saturated brine
  5. dry with materialthen dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified via prep HPLC under neutral condition

Sources & evidence

ORD record
ord-d450f33b60454048a5e079a183888aaf
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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