Acetic Acid → HCID 178514783, compound

HRID 69794Notes

Reaction equation

HRID 69794 reaction equation
I.[NH2:2][CH2:3][CH2:4][NH:5][C:6]1[C:7]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)C(=O)[O:13][N:12]=2)=[N:8][O:9][N:10]=1.Cl[S:28]([NH:31]C(=O)OC(C)(C)C)(=[O:30])=[O:29].C(N(CC)CC)C.FC(F)(F)C(O)=O.[OH-].[Na+].O.C(O)(=O)C>ClCCl>[NH2:31][S:28]([NH:2][CH2:3][CH2:4][NH:5][C:6]1[C:7]([C:11](=[N:12][OH:13])[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=2)=[N:8][O:9][N:10]=1)(=[O:30])=[O:29]

Participants

9

Reactant 7

HCID 176Acetic AcidHCID 962WaterHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 15677406tert-butyl N-(chlorosulfonyl)carbamateHCID 666058333-{4-[(2-Aminoethyl)amino]-1,2,5-oxadiazol-3-yl}-4-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)-one hydroiodide

Product 1

HCID 178514783HCID 178514783, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a separate flask, 3-{4[(2-aminoethyl)amino]-1,2,5-oxadiazol-3-yl}-4-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)-one hydroiodide (26 mg, 0.053 mmol) was suspended in dichloromethane (0.5 mL). A nitrogen atmosphere was established and the temperature brought to 0° C. The tert-butyl [chlorosulfonyl]carbamate solution (prepared as above) was added over 5 minutes to the stirred suspension of the amine salt. After 10 minutes, triethylamine (37 μL, 0.27 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1.5 hours. After concentrating in vacuo, the residue was treated with trifluoroacetic acid (0.5 mL, 6 mmol). This was stirred for 1 hour and the mixture was again concentrated to dryness in vacuo. The dried solids were suspended in methanol (0.5 mL) and a 2.0 N NaOH in water (0.53 mL, 1.1 mmol) was added in one portion. The reaction was heated to 45° C. and stirred for 30 minutes. After neutralization with acetic acid (60 μL, 1.1 mmol), the product was purified by preparative LCMS to give the desired product (8.5 mg, 39%). LCMS calculated for C12H15F3N7O4S (M+H)+: m/z=410.0. 1H NMR (400 MHz, CD3OD): δ 7.36 (t, J=7.8 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.10 (s, 1H), 7.03 (d, J=7.8 Hz, 1H), 3.48 (m, 2H), 3.29 (m, 2H).

Workup

  1. custombrought to 0° C
  2. concentrationAfter concentrating in vacuo
  3. stirringThis was stirred for 1 hour
  4. concentrationthe mixture was again concentrated to dryness in vacuo
  5. temperatureThe reaction was heated to 45° C.
  6. stirringstirred for 30 minutes

Sources & evidence

ORD record
ord-b33b926a478e41068e189bdd9ffa0c0d
Source dataset
uspto-grants-2014_09
Patent number
US08822511B2

Reaction notes

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