1-Chloro-3-iodobenzene → HCID 178463852, compound

HRID 1011924Notes

Reaction equation

HRID 1011924 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[CH:3]=1.[CH2:9]([N:11]([CH2:33][CH3:34])[CH:12]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[C:23]([CH3:24])=[C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]#[CH:32])[CH:26]=3)[NH:21][N:20]=2)=[O:18])[CH2:13]1)[CH3:10]>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]([C:32]#[C:31][C:27]2[CH:26]=[C:25]([C:22]3[NH:21][N:20]=[C:19]([C:17]([N:14]4[CH2:15][CH2:16][CH:12]([N:11]([CH2:33][CH3:34])[CH2:9][CH3:10])[CH2:13]4)=[O:18])[C:23]=3[CH3:24])[CH:30]=[CH:29][CH:28]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 122691-Chloro-3-iodobenzeneHCID 178436202(3-Diethylamino-pyrrolidin-1-yl)-[5-(3-ethynyl-phenyl)-4-methyl-1H-pyrazol-3-yl]-methanone

Product 1

HCID 178463852HCID 178463852, compoundYield 65.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 0.086 g (0.36 mmol) of 1-chloro-3-iodobenzene in 1.5 ml piperidine was degassed (argon) and treated with 17 mg (0.01 mmol) Pd(PPh3)4 and 3 mg (0.01 mmol) CuI. The reaction mixture was stirred at 50° C. for 10 min and then slowly (60 min) treated with 0.105 g (0.30 mmol) of (3-diethylamino-pyrrolidin-1-yl)-[5-(3-ethynyl-phenyl)-4-methyl-1H-pyrazol-3-yl]-methanone in 1.55 ml piperidine. After 30 min the bath was slowly (30 min) heated to 80° C. The reaction mixture was stirred at this temperature for 1 h and then partitioned between chilled water sat. KHCO3/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Purification by flash-chromatography on silica gel (CH2Cl2/MeOH 97.5:2.5 to 95:5) yielded 0.090 g (65%) of the title compound as light yellow foam. MS: 461.1 (MH+, 1 Cl).

Workup

  1. waitAfter 30 min the bath was slowly
  2. temperature(30 min) heated to 80° C
  3. stirringThe reaction mixture was stirred at this temperature for 1 h
  4. custompartitioned
  5. temperaturebetween chilled water sat. KHCO3/Et2O (3×)
  6. washThe organic phases were washed with aqueous 10% NaCl
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customPurification by flash-chromatography on silica gel (CH2Cl2/MeOH 97.5:2.5 to 95:5)

Sources & evidence

ORD record
ord-c25c82e94ab14e96805c8fb67ae3fe09
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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