Hydrochloric Acid → {2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-ethyl}-urea

HRID 217304

Reaction equation

HRID 217304 reaction equation
S.[Na].Cl.[Cl:4][C:5]1[C:6]([C:18]2[CH:23]=[C:22]([S:24]([CH3:26])=O)[N:21]=[C:20]([NH2:27])[N:19]=2)=[C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]2=[C:9]([CH:17]=1)[CH2:10][O:11][CH2:12]3.C(N(CC)C(C)C)(C)C.ClC[CH2:39][NH:40][C:41]([NH2:43])=[O:42]>CN(C)C=O.C(OC(=O)C)C>[NH2:27][C:20]1[N:21]=[C:22]([S:24][CH2:26][CH2:39][NH:40][C:41]([NH2:43])=[O:42])[CH:23]=[C:18]([C:6]2[C:5]([Cl:4])=[CH:17][C:9]3[CH2:10][O:11][CH2:12][C:13]4[C:8]=3[C:7]=2[CH:16]=[CH:15][CH:14]=4)[N:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 240817N-(2-Chloroethyl)ureaHCID 578987824-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamineHCID 86586439Sodium hydrogen sulphide

Product 1

HCID 57898649{2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-ethyl}-ureaYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydrogen sulfide (1.07 g) was dissolved in N,N-dimethylformamide (25 ml). To the mixture was added 4N hydrogen chloride in ethylacetate (13.3 ml) at room temperature. After stirring for approximately 30 minutes at the same temperature, to the resulting mixture were added 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine (1.20 g) obtained in Step 5 of Example 314 and N,N-diisopropylethylamine (2.9 ml) successively. The mixture was stirred at 80° C. for four hours, and then the mixture was allowed to cool to room temperature. To the mixture were added to 2-chloro-ethylurea (3.20 g), N,N-diisopropylethylamine (5.8 ml) and N,N-dimethylformamide (15 ml) successively. The reaction mixture was stirred at 80° C. for 14 hours and then allowed to cool to room temperature. The reaction was quenched by adding water and extracted with ethyl acetate. The organic layer was separated, washed with water and brine subsequently, dried over anhydrous sodium sulfate. After removal of inorganic salts, the solution was concentrated by evaporation. The resulting residue was purified by HPLC (column; ODS, mobile phase; 0.05% TFA in water: 0.05% TFA in acetonitrile=65:35) to give {2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-ethyl}-urea (0.93 g).

Workup

  1. stirringThe mixture was stirred at 80° C. for four hours
  2. stirringThe reaction mixture was stirred at 80° C. for 14 hours
  3. temperatureto cool to room temperature
  4. customThe reaction was quenched
  5. additionby adding water
  6. extractionextracted with ethyl acetate
  7. customThe organic layer was separated
  8. washwashed with water and brine subsequently
  9. dry with materialdried over anhydrous sodium sulfate
  10. customAfter removal of inorganic salts
  11. concentrationthe solution was concentrated by evaporation
  12. customThe resulting residue was purified by HPLC (column; ODS, mobile phase; 0.05% TFA in water: 0.05% TFA in acetonitrile=65:35)

Sources & evidence

ORD record
ord-a6d14586979f4c1697c286968cbca98b
Source dataset
uspto-grants-2012_06
Patent number
US08193351B2

Linked notes

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