Hydrochloric Acid → 3-(4-((2-Aminoethyl)amino)-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydrochloride

HRID 631102Notes

Reaction equation

HRID 631102 reaction equation
[ClH:1].[Br:2][C:3]1[CH:4]=[C:5]([N:10]2[C:14](=[O:15])[O:13][N:12]=[C:11]2[C:16]2[C:17]([NH:21][CH2:22][CH2:23][NH:24]C(=O)OC(C)(C)C)=[N:18][O:19][N:20]=2)[CH:6]=[CH:7][C:8]=1[F:9]>C(OCC)(=O)C>[ClH:1].[NH2:24][CH2:23][CH2:22][NH:21][C:17]1[C:16]([C:11]2[N:10]([C:5]3[CH:6]=[CH:7][C:8]([F:9])=[C:3]([Br:2])[CH:4]=3)[C:14](=[O:15])[O:13][N:12]=2)=[N:20][O:19][N:18]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66605739tert-Butyl (2-((4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-yl)amino)ethyl)carbamate

Product 1

HCID 666064613-(4-((2-Aminoethyl)amino)-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydrochlorideYield 248.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 22 L flask was charged hydrogen chloride (4 N solution in 1,4-dioxane, 4 L, 16 mol). tert-Butyl [2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]carbamate (2315 g, 4.77 mol) was added as a solid in portions over 10 min. The slurry was stirred at room temperature and gradually became a thick paste that could not be stirred. After sitting overnight at room temperature, the paste was slurried in ethyl acetate (10 L), filtered, re-slurried in ethyl acetate (5 L), filtered, and dried to a constant weight to afford the desired product as a white solid (combined with other runs, 5 kg starting material charged, 4113 g, 95%). LCMS for C12H11BrFN6O3 (M+H)+: m/z=384.9, 386.9. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (m, 4H), 7.76 (m, 1H), 7.58 (t, J=8.7 Hz, 1H), 6.78 (t, J=6.1 Hz, 1H), 3.51 (dd, J=11.8, 6.1 Hz, 2H), 3.02 (m, 2H).

Workup

  1. stirringbe stirred
  2. filtrationfiltered, re-slurried in ethyl acetate (5 L)
  3. filtrationfiltered
  4. customdried to a constant weight

Sources & evidence

ORD record
ord-ea087add73fd47b48353d0daf890ad74
Source dataset
uspto-grants-2016_04
Patent number
US09320732B2

Reaction notes

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