Chloroacetyl chloride → HCID 178480920、化合物

HRID 1273064ノート

反応式

HRID 1273064 の反応式
O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[CH:44][CH:45]=2)=[N:8]1.Cl[CH2:48][C:49](Cl)=[O:50].C(N(CC)C(C)C)(C)C.[CH3:61][N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1>O1CCCC1.O>[NH:18]1[CH:19]=[N:20][C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([NH:46][C:49](=[O:50])[CH2:48][N:65]3[CH2:66][CH2:67][N:62]([CH3:61])[CH2:63][CH2:64]3)[CH:43]=[CH:44][CH:45]=2)=[N:17]1

参加物

7

反応物 4

HCID 6577Chloroacetyl chlorideHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 211011823-(1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenylamine

生成物 1

HCID 178480920HCID 178480920、化合物収率 54.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenylamine (0400 g, 0.66 mmol) in tetrahydrofuran (4 mL) was added 2-chloroacetyl chloride (0.083 mL, 1.0 mmol) followed by N,N-diisopropylethylamine (0.116 mL, 0.66 mmol). The reaction was stirred at room temperature for 4 h. Water (20 mL) was added and the reaction mixture was extracted with ethyl acetate. The combined organic organic extracts were dried over anhydrous sodium sulfate, filtered and evaporated. The residue was dissolved in N,N-dimethylformamide (5 mL) and N-methylpiperazine (0.320 mL, 3.3 mmol) was added. The mixture was stirred at room temperature for 14 h. Water (30 mL) was added and the mixture extracted with ethyl acetate. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and evaporated. The residue was dissolved in 4 N hydrochloric acid in 1,4-dioxane (10 mL) and the mixture was stirred at room temperature for 2 h. Dioxane was removed with a rotary evaporator and the residue was purified by preparative HPLC. The desired fractions were neutralized with ammonium hydroxide, extracted with butanol and evaporated to give the title compound (0.150 g, 54% yield): 1H NMR (DMSO-d6) δ 13.45 (br s, 1H), 10.04 (s, 1H), 8.73 (s, 1H), 8.34 (d, 2H), 8.10 (d, 1H), 7.75 (d, 1H), 7.69 (d, 2H), 7.48 (t, 1H), 2.15 (s, 3H), 1.80 (m, 8H), 1.33 (s, 3H). ES-MS (m/z) 417 [M+1]+.

後処理

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. dry with materialThe combined organic organic extracts were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (5 mL)
  6. stirringThe mixture was stirred at room temperature for 14 h
  7. extractionthe mixture extracted with ethyl acetate
  8. dry with materialThe combined organic fractions were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. dissolutionThe residue was dissolved in 4 N hydrochloric acid in 1,4-dioxane (10 mL)
  12. stirringthe mixture was stirred at room temperature for 2 h
  13. customDioxane was removed with a rotary evaporator
  14. customthe residue was purified by preparative HPLC
  15. extractionextracted with butanol
  16. customevaporated

出典と根拠

ORDレコード
ord-a4d4e22c64844aa7a89b7d1c7a1e6812
出典データセット
uspto-grants-2007_04
特許番号
US07208513B2

反応ノート

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