Hydrochloric Acid → 5-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amine

HRID 2284771Notes

Reaction equation

HRID 2284771 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5]([C:12]#[C:13][CH2:14][CH2:15][CH2:16][N:17]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:4][N:3]=1.Cl>C(O)C.O1CCCC1.O.NN>[NH2:17][CH2:16][CH2:15][CH2:14][C:13]#[C:12][C:5]1[C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 900521562-(5-(2-Chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Product 1

HCID 900521545-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amineYield 38.6%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 2-(5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (K1, 2.0 g) in ethanol (15 mL) and tetrahydrofuran (15 mL), hydrazine monohydrate (2.6 mL) was added at room temperature, and the mixture was stirred at the same temperature for 3 hours and 30 minutes. The reaction mixture was cooled on ice, and then neutralized by adding 1.0 mol/L aqueous hydrochloric acid. The insoluble matter was removed by filtration, and then water and ethyl acetate were added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with saturated aqueous sodium hydrogencarbonate, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 93% ethyl acetate in methanol) to obtain oily 5-(5-amino-1-pentyn-1-yl)-2-chloro-N-propylpyrimidin-4-amine (K2, 510 mg).

Workup

  1. temperatureThe reaction mixture was cooled on ice
  2. customThe insoluble matter was removed by filtration
  3. additionwater and ethyl acetate were added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed with saturated aqueous sodium hydrogencarbonate
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 93% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-6e44c4bb29ad46a582319617a86be3f9
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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