Phosphorus oxychloride → 2-(5-(4-Chloro-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

HRID 2284757Notes

Reaction equation

HRID 2284757 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13](O)[C:12]([C:16]#[C:17][CH2:18][CH2:19][CH2:20][N:21]3[C:29](=[O:30])[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22]3=[O:31])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.P(Cl)(Cl)([Cl:34])=O>C(OCC)(=O)C>[Cl:34][C:13]1[C:12]([C:16]#[C:17][CH2:18][CH2:19][CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[CH:11][N:10]=[C:9]([NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[N:14]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178514994HCID 178514994, compound

Product 1

HCID 900523502-(5-(4-Chloro-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 2-(5-(2-((3-fluorophenyl)amino)-4-hydroxypyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J4, 36 mg), phosphorus oxychloride (1 mL) was added at room temperature, and the mixture was stirred at 80° C. for 45 minutes. The reaction mixture was cooled to room temperature, and then poured into ice, and then ethyl acetate was added to the mixture. The organic layer was separated, washed successively with water, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid matter was washed with diisopropyl ether, and then dried under reduced pressure to obtain 2-(5-(4-chloro-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J5, 21 mg) as pale yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionpoured into ice
  3. customThe organic layer was separated
  4. washwashed successively with water, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. washThe obtained solid matter was washed with diisopropyl ether
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-56a210e8aa0d494da22985f5176933d4
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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