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

HRID 219908노트

반응식

HRID 219908 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-acf0198879924c0aa776729dfa40628e
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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