2-Methoxyethylamine → HCID 178495857, compound

HRID 513833Notes

Reaction equation

HRID 513833 reaction equation
N1CCC[C@H]1C(O)=O.[NH2:9][C:10]1[N:14]([C:15]2[CH:24]=[CH:23][C:18]3[NH:19][C:20]([CH3:22])=[N:21][C:17]=3[CH:16]=2)[N:13]=[CH:12][C:11]=1[C:25]([C:27]1[N:28]([S:37]([C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)(=[O:39])=[O:38])[C:29]2[C:34]([CH:35]=1)=[CH:33][CH:32]=[C:31](I)[CH:30]=2)=[O:26].N12CCCN=C1CCCCC2.[CH3:58][O:59][CH2:60][CH2:61][NH2:62].O.N>CS(C)=O.[Cu]I>[NH2:9][C:10]1[N:14]([C:15]2[CH:24]=[CH:23][C:18]3[NH:19][C:20]([CH3:22])=[N:21][C:17]=3[CH:16]=2)[N:13]=[CH:12][C:11]=1[C:25]([C:27]1[N:28]([S:37]([C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)(=[O:39])=[O:38])[C:29]2[C:34]([CH:35]=1)=[C:33]([NH:62][CH2:61][CH2:60][O:59][CH3:58])[CH:32]=[CH:31][CH:30]=2)=[O:26]

Participants

8

Reactant 5

HCID 80182-MethoxyethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 145742L-ProlineHCID 12896473Azane;hydrateHCID 178427388HCID 178427388, compound

Product 1

HCID 178495857HCID 178495857, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Copper (I) iodide (16 mg, 0.086 mmol), L-proline (37 mg, 0.32 mmol), and [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-iodo-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone (104 mg) were dissolved in anhydrous dimethylsulfoxide (DMSO), and then 1,8-diazabicyclo[5.4.0]undec-7-ene (49 μl) and 2-methoxyethylamine (43 μl) were added thereto. The mixture was heated at 80° C. with stirring under a nitrogen atmosphere for 18 hours. After the reaction mixture was cooled to room temperature, 25% ammonia water was added thereto. The resulting mixture was extracted with ethyl acetate. The organic layer was isolated, washed with an aqueous solution of 1 M hydrochloric acid and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography (dichloromethane/methanol=100/5) using a small amount of silica gel to give crude product of [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[4-(2-methoxy-ethylamino)-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone. The obtained crude product was used in subsequent reactions without purification.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. extractionThe resulting mixture was extracted with ethyl acetate
  3. customThe organic layer was isolated
  4. washwashed with an aqueous solution of 1 M hydrochloric acid
  5. dry with materialwith a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate
  6. customAfter the desiccant was removed by filtration
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe resulting residue was purified by chromatography (dichloromethane/methanol=100/5)

Sources & evidence

ORD record
ord-3498272740b64d888fe3f735ddb3e0d0
Source dataset
uspto-grants-2015_08
Patent number
US09102692B2

Reaction notes

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