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

HRID 217304

反応式

HRID 217304 の反応式
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

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a6d14586979f4c1697c286968cbca98b
出典データセット
uspto-grants-2012_06
特許番号
US08193351B2

関連ノート

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