3-Methoxypropylamine → 2-(5-(2-((3-Fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

HRID 2284758Notes

Reaction equation

HRID 2284758 reaction equation
Cl[C:2]1[C:7]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:6][N:5]=[C:4]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=2)[N:3]=1.C(N(CC)CC)C.[CH3:39][O:40][CH2:41][CH2:42][CH2:43][NH2:44].C(OCC)(=O)C>O1CCOCC1.O>[F:31][C:27]1[CH:26]=[C:25]([NH:24][C:4]2[N:3]=[C:2]([NH:44][CH2:43][CH2:42][CH2:41][O:40][CH3:39])[C:7]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][N:13]3[C:21](=[O:22])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]3=[O:23])=[CH:6][N:5]=2)[CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 16723-MethoxypropylamineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 900523502-(5-(4-Chloro-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Product 1

HCID 900523172-(5-(2-((3-Fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(5-(4-chloro-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J5, 124 mg) in 1,4-dioxane (2 mL), triethylamine (119 μL) and 3-methoxypropylamine (88 μL) were added at room temperature, and the mixture was stirred overnight at 50° C. in a sealed tube. The reaction mixture was cooled to room temperature, and then ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 2-(5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J6, 90 mg) as pale yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-de2af69fc4804799b37d86c03dce2fd4
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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