tert-Butanol → N-[2-({4-[4-(3-Chloro-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide

HRID 415820Notes

Reaction equation

HRID 415820 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].C(O)(C)(C)C.Cl.[NH2:14][CH2:15][CH2:16][NH:17][C:18]1[C:19]([C:23]2[N:27]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[C:30]([Cl:35])[CH:29]=3)[C:26](=[O:36])[O:25][N:24]=2)=[N:20][O:21][N:22]=1.C(N(CC)CC)C>ClCCl.Cl>[Cl:35][C:30]1[CH:29]=[C:28]([N:27]2[C:26](=[O:36])[O:25][N:24]=[C:23]2[C:19]2[C:18]([NH:17][CH2:16][CH2:15][NH:14][S:2]([NH2:5])(=[O:4])=[O:3])=[N:22][O:21][N:20]=2)[CH:33]=[CH:32][C:31]=1[F:34]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 666059023-{4-[(2-Aminoethyl)amino]-1,2,5-oxadiazol-3-yl}-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydrochloride

Product 1

HCID 66606394N-[2-({4-[4-(3-Chloro-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamideYield 80.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

A solution of chlorosulfonyl isocyanate (2.0 mL, 23 mmol) in dichloromethane (70 mL) was treated with t-butyl alcohol (2.2 mL, 23 mmol) at 0° C. and stirred at 25° C. for 1 h. This mixture was added to a suspension of 3-{4-[(2-aminoethyl)amino]-1,2,5-oxadiazol-3-yl}-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydrochloride (4.3 g, 11 mmol) in dichloromethane (70 mL). The reaction mixture was treated with a solution of triethylamine (6.3 mL, 45 mmol) in dichloromethane (20 mL) at 0° C. and stirred at 25° C. for 3 h. The reaction mixture was diluted with 0.1 N HCl and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to a white solid. The white solid was diluted with dichloromethane (100 mL), treated with trifluoroacetic acid (20 mL), and stirred at 25° C. for 3 h. The reaction mixture was concentrated to a crude residue that was purified by silica gel chromatography to give the desired product (3.7 g, 78%) as a white solid. LCMS for C12H12ClFN7O5S (M+H)+: m/z=420.0. 1H NMR (300 MHz, DMSO-d6): δ 7.98 (dd, J=6.4, 2.1 Hz, 1H), 7.70-7.60 (m, 2H), 6.66 (t, J=5.9 Hz, 1H), 6.57 (s, 2H), 6.52 (t, J=5.9 Hz, 1H), 3.42-3.35 (m, 2H), 3.13-3.06 (m, 2H).

Workup

  1. stirringstirred at 25° C. for 3 h
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. washThe combined organic layers were washed with brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a white solid
  7. additionThe white solid was diluted with dichloromethane (100 mL)
  8. additiontreated with trifluoroacetic acid (20 mL)
  9. stirringstirred at 25° C. for 3 h
  10. concentrationThe reaction mixture was concentrated to a crude residue that
  11. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-f312d3ae164c4cc1b162f3bf27de1242
Source dataset
uspto-grants-2012_01
Patent number
US08088803B2

Reaction notes

Loading…