Benzoic Acid → HCID 178526364, compound

HRID 2097619Notes

Reaction equation

HRID 2097619 reaction equation
[C:1](O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][CH2:11][C:12]1[C:13]([C:17]2[N:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=3)C(=O)[O:19][N:18]=2)=[N:14][O:15][N:16]=1.CCN(C(C)C)C(C)C>C(#N)C.C(Cl)Cl.CN(C1C=CN=CC=1)C.CO>[CH2:1]([NH:10][CH2:11][C:12]1[C:13]([C:17](=[N:18][OH:19])[NH:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=2)=[N:14][O:15][N:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 243Benzoic AcidHCID 81531Diisopropylethylamine2×HCID 589418433-[4-(Aminomethyl)-1,2,5-oxadiazol-3-yl]-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 178526364HCID 178526364, compoundYield 9.1%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Benzoic acid (4.3 mg, 0.035 mmol) and 3-[4-(aminomethyl)-1,2,5-oxadiazol-3-yl]-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (10 mg, 0.032 mmol) was dissolved in ACN (0.2 mL) and DCM (0.2 mL). To the mixture was added DMAP (2.4 mg, 0.02 mmol) and DIPEA (17 μL, 0.096 mmol). After the mixture became a clear solution, bromotris(pyrrolydino)phophonium hexafluorophosphate (16 mg, 0.035 mmol) was added, followed by additional DIPEA (17 μL, 0.0962 mmol). The reaction mixture was stirred at rt for 6 hrs. LCMS indicated ˜70% ratio of product to starting amine. The reaction was then diluted with MeOH and crude residue was purified by preparative LCMS. The intermediate was stripped to dryness, redissolved in EtOH (1 mL) and 1 M of sodium hydroxide in water (0.06 mL). The reaction was stirred for 1 hr at rt. The reaction was quenched with acetic acid and then diluted with MeOH and crude residue was purified by preparative LCMS to afford the desired product (1.1 mg). MF═C17H13ClFN5O3; LCMS calculated for C17H14ClFN5O3(M+H)+: m/z=390.077.

Workup

  1. additionwas added
  2. customwas purified by preparative LCMS
  3. dissolutionredissolved in EtOH (1 mL)
  4. stirringThe reaction was stirred for 1 hr at rt
  5. customThe reaction was quenched with acetic acid
  6. additiondiluted with MeOH and crude residue
  7. customwas purified by preparative LCMS

Sources & evidence

ORD record
ord-d56ccd4804fc4f52a6909507f6cad549
Source dataset
uspto-grants-2013_05
Patent number
US08450351B2

Reaction notes

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