Triethylamine → 3-(2,2-Dimethyl-propyl)-5-(4-fluoro-phenylethyl)-3H-imidazo[4,5-b]pyridin-2-ylamine

HRID 730021Notes

Reaction equation

HRID 730021 reaction equation
C(N(CC)CC)C.[Br-].Br[C:10]1[N:15]=[C:14]2[N:16]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:17]([NH3+:19])=[N:18][C:13]2=[CH:12][CH:11]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[CH:33])=[CH:28][CH:27]=1>C(O)C.C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:22][C:21]([CH3:24])([CH3:23])[CH2:20][N:16]1[C:14]2=[N:15][C:10]([CH2:33][CH2:32][C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=3)=[CH:11][CH:12]=[C:13]2[N:18]=[C:17]1[NH2:19]

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 5226271-Ethynyl-4-fluorobenzene2×HCID 178446125HCID 178446125, compound

Product 1

HCID 688682873-(2,2-Dimethyl-propyl)-5-(4-fluoro-phenylethyl)-3H-imidazo[4,5-b]pyridin-2-ylamineYield 87%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
72.5 °C

Procedure

Add triethylamine (27.10 g, 267.80 mmol) to a mixture of 5-bromo-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-2-yl-ammonium bromide (25.00 g, 68.67 mmol) in ethanol (25 mL) and toluene (75 mL). Heat to 70-75° C. and then add Pd(OAc)2 (0.15 g, 0.69 mmol), triphenylphosphine (0.72 g, 2.75 mmol), and copper (I) iodide (0.13 g, 0.69 mmol). Add ⅔ of a solution of 4-fluorophenylacetylene (12.37 g, 103.00 mmol) in toluene (50 mL, 2.0 vol.) over 15 minutes. Add the remaining 4-fluoroacetylene solution after 1 h. After 3 h, add additional 4-fluorophenylacetylene (1.5 g, 12.86 mmol). After an additional hour, remove EtOH by distillation. Cool the reaction mixture to <40° C. and add water (25 mL). Cool to room temperature. Filter suspension and wash with water (25 mL) and 2×25 mL toluene. Dry under reduced pressure at 45-50° C. to provide 19.3 g (87%) of the desired compound.

Workup

  1. waitAfter an additional hour
  2. customremove EtOH
  3. distillationby distillation
  4. temperatureCool the reaction mixture to <40° C.
  5. additionadd water (25 mL)
  6. temperatureCool to room temperature
  7. filtrationFilter suspension
  8. washwash with water (25 mL) and 2×25 mL toluene
  9. customDry under reduced pressure at 45-50° C.

Sources & evidence

ORD record
ord-d9e79a0e94e748609b40263110a42044
Source dataset
uspto-grants-2009_09
Patent number
US07582652B2

Reaction notes

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