Water → HCID 11574295, compound

HRID 1170500Notes

Reaction equation

HRID 1170500 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.[N:12]1([C:17]2[N:21]=[C:20]([C:22](=O)[CH3:23])[S:19][N:18]=2)[CH:16]=[CH:15][N:14]=[CH:13]1.C(OC(=O)[N:31]([CH2:42][CH2:43][NH2:44])[CH2:32][C:33]1[CH:41]=[CH:40][C:36]2[O:37][CH2:38][O:39][C:35]=2[CH:34]=1)(C)(C)C.O>O1CCOCC1.C(O)(C(F)(F)F)=O.C(Cl)Cl.CCOC(C)=O>[O:37]1[C:36]2[CH:40]=[CH:41][C:33]([CH2:32][NH:31][CH2:42][CH2:43][NH:44][CH:22]([C:20]3[S:19][N:18]=[C:17]([N:12]4[CH:16]=[CH:15][N:14]=[CH:13]4)[N:21]=3)[CH3:23])=[CH:34][C:35]=2[O:39][CH2:38]1

Participants

8

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 58654355HCID 58654355, compoundHCID 68695742HCID 68695742, compound

Product 1

HCID 11574295HCID 11574295, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
67.5 °C

Procedure

A catalytic amount of TsOH (20 mg) was added to a solution of 1-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-ethanone obtained from Step 1 (233 mg, 1.20 mmol) and (2-amino-ethyl)-benzo[1,3]dioxol-5-ylmethyl-carbamic acid tert-butyl ester (565 mg, 1.92 mmol) in 1,4-dioxane (10 mL) under a nitrogen atmosphere at r.t. prior to heating at 65-70° C. for 4 h. The reaction was then cooled to r.t. and NaHB(OAc)3 (763 mg, 3.60 mmol) was added. After stirring for an additional hour, water was added and the solution was extracted with ethyl acetate (2×70 mL), washed with brine and dried over Na2SO4. Evaporation of the solvent gave a yellow residue which was dissolved in TFA/DCM (1:1, 6 mL) and stirred at room temperature for 30 min. The solvent was evaporated to afford a yellow solid. The crude product was diluted with EtOAc (100 mL), washed with 1M NaOH (50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to an orange solid. Purification was achieved using column chromatography (CH2Cl2 to 4:1 CH2Cl2/MeOH) to afford 31 mg (7%) of N-benzo[1,3]dioxol-5-ylmethyl-N′-[1-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-ethyl]-ethane-1,2-diamine as a white solid. [M+H]+ 372.97; 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.74 (s, 1H), 7.13 (s, 1H), 6.84 (s, 1H), 6.76 (m, 2H), 5.93 (s, 2H), 4.12 (q, 1H), 3.73 (d, 2H), 2.91-2.77 (m, 4H), 2.19 (br s, 2H), 1.54 (d, 3H).

Workup

  1. temperatureThe reaction was then cooled to r.t.
  2. extractionthe solution was extracted with ethyl acetate (2×70 mL)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customEvaporation of the solvent
  6. customgave a yellow residue which
  7. stirringstirred at room temperature for 30 min
  8. customThe solvent was evaporated
  9. customto afford a yellow solid
  10. washwashed with 1M NaOH (50 mL), brine (50 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to an orange solid
  14. customPurification

Sources & evidence

ORD record
ord-5b4c4731339846569b6bd564d8d59801
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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