Chloroacetyl chloride → HCID 178480920, compound

HRID 1353968Notes

Reaction equation

HRID 1353968 reaction equation
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

Participants

7

Reactant 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

Product 1

HCID 178480920HCID 178480920, compoundYield 54.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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 (0.400 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]+.

Workup

  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

Sources & evidence

ORD record
ord-a353082d1de8434997141c55349b22b8
Source dataset
uspto-grants-2007_05
Patent number
US07220771B2

Reaction notes

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