Ethyl Acetate → 5-(5-amino-1-pentyn-1-yl)-N2-(3-fluorophenyl)-N4-(3-methoxypropyl)pyrimidine-2,4-diamine

HRID 2284759Notes

Reaction equation

HRID 2284759 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])[C:12]([C:21]#[C:22][CH2:23][CH2:24][CH2:25][N:26]3C(=O)C4C(=CC=CC=4)C3=O)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.C(OCC)(=O)C>O1CCCC1.C(O)C.O.NN>[NH2:26][CH2:25][CH2:24][CH2:23][C:22]#[C:21][C:12]1[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[N:14][C:9]([NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:10][CH:11]=1

Participants

6

Reactant 2

HCID 8857Ethyl AcetateHCID 900523172-(5-(2-((3-Fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Product 1

HCID 900521525-(5-amino-1-pentyn-1-yl)-N2-(3-fluorophenyl)-N4-(3-methoxypropyl)pyrimidine-2,4-diamineYield 83.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 24654Hydrazine hydrate (1:1)Solvent

Procedure

To a solution of 2-(5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J6, 90 mg) in tetrahydrofuran (1 mL) and ethanol (0.5 mL), hydrazine monohydrate (100 μL) was added at room temperature, and the mixture was stirred for 1 hour under reflux by heating. The reaction mixture was cooled to room temperature, and then ethyl acetate was added to the reaction mixture. The insoluble matter was removed by filtration, and then 1.0 mol/L aqueous hydrochloric acid was added to the reaction mixture until the mixture became acidic. The aqueous layer was separated, 3.0 mol/L aqueous sodium hydroxide was added until the mixture became basic, and the reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 5-(5-amino-1-pentyn-1-yl)-N2-(3-fluorophenyl)-N4-(3-methoxypropyl)pyrimidine-2,4-diamine (J7, 55 mg) as pale yellow solid.

Workup

  1. temperatureunder reflux
  2. temperatureby heating
  3. customThe insoluble matter was removed by filtration
  4. addition1.0 mol/L aqueous hydrochloric acid was added to the reaction mixture until the mixture
  5. customThe aqueous layer was separated
  6. addition3.0 mol/L aqueous sodium hydroxide was added until the mixture
  7. extractionthe reaction mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-a76734776ba7450aaba6393033596f7c
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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