Nitrogen → Methyl 4-[3-(2,2'-dimethylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

HRID 219908Notes

Reaction equation

HRID 219908 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6](C(O)=O)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17].[NH2:18][C:19](=[N:31][OH:32])[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([F:30])[CH:21]=1.Cl.[CH2:34](N=C=NCCCN(C)C)C.N#N.C(N(C(C)C)C(C)C)C>C1COCC1.CC#N>[CH3:17][C:12]1[CH:13]=[C:14]([C:19]2([C:20]3[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([F:30])[CH:21]=3)[N:18]=[CH:34][O:32][NH:31]2)[CH:15]=[CH:16][C:11]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1]

Participants

8

Reactant 5

HCID 947NitrogenHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219373032,2'-Dimethyl-[1,1'-biphenyl]-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

Product 1

HCID 67542198Methyl 4-[3-(2,2'-dimethylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 3 (814 mg; 3.60 mmol; 1.20 eq.), Intermediate 1 (637 mg; 3 mmol; 1 eq.) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (690 mg; 3.60 mmol; 1.20 eq.) were dissolved in THF (10 mL) and CH3CN (10 mL) in a 20 mL microwave vial under N2. The reaction mixture was stirred overnight at RT. Then n-ethyldiisopropylamine (DIEA) (1.22 mL; 7.20 mmol; 2.40 eq.) was added and the mixture was heated in the microwave at 150° C. for 30 min. The reaction mixture was evaporated to dryness. EtOAc (50 mL) was added and the mixture was washed with HCl 0.1 N (2×25 mL), a saturated aqueous solution of NaHCO3 (25 mL) and dried over MgSO4. After evaporation of the solvents, the resulting crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound as a white powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.17-8.16 (m, 1H), 8.12 (d, J=7.2 Hz, 1H), 8.29-8.04 (m, 2H), 7.98 (dd, J=11.1, 2.5 Hz, 1H), 7.39-7.27 (m, 4H), 7.14-7.11 (m, 1H), 3.91 (s, 3H), 2.13 (s, 3H), 2.03 (s, 3H). LC/MS (Method A): 403.0 (M+H)+. HPLC (Method A) Rt 6.23 min (Purity: 93.5%).

Workup

  1. temperaturethe mixture was heated in the microwave at 150° C. for 30 min
  2. customThe reaction mixture was evaporated to dryness
  3. additionEtOAc (50 mL) was added
  4. washthe mixture was washed with HCl 0.1 N (2×25 mL)
  5. dry with materiala saturated aqueous solution of NaHCO3 (25 mL) and dried over MgSO4
  6. customAfter evaporation of the solvents
  7. customthe resulting crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5)

Sources & evidence

ORD record
ord-acf0198879924c0aa776729dfa40628e
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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