Dimethylformamide → Methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

HRID 219916노트

반응식

HRID 219916 반응식
[CH3:1][O:2][CH2:3][C:4]1[CH:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:31][C:32](=[N:44]O)[C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[C:35]([F:43])[CH:34]=1>C1(C)C=CC=CC=1>[F:43][C:35]1[CH:34]=[C:33]([C:32]2[N:31]=[C:10]([C:8]3[CH:7]=[CH:6][C:5]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=3)[O:12][N:44]=2)[CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

생성물 1

HCID 66678608Methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate수율 82.7%

시약·촉매·용매 1

HCID 1140Toluene용매3회

실험 절차

Intermediate 28 (4 g; 15.61 mmol) was dissolved in dry Toluene (60 mL) under N2 at RT, then oxalyl chloride (1.98 mL; 23.41 mmol) was added in one portion and then DMF (24.02 μl) was added. The reaction mixture was stirred at RT for 3 hours. The reaction mixture was concentrated to afford a yellow liquid. To a flask containing Intermediate 1 (3.31 g; 15.61 mmol) in Py (20 mL; 5 V) and toluene (20 mL) at RT and under N2 was added dropwise the yellow liquid obtained previously in toluene (40 mL), the addition took 15 min. The reaction mixture was stirred at RT for 12 hours. Then the mixture was refluxed for 24 hours. The reaction mixture was cooled to RT and concentrated affording a beige solid which was washed with MeOH (40 mL). The suspension was filtered affording the title compound as a beige solid (5.58 g, 82%). 1H NMR (DMSO-d6, 300 MHz) δ 8.33 (m, 1H), 8.19-7.98 (m, 4H), 7.44-7.28 (m, 4H), 7.16-7.13 (m, 1H), 4.24-4.14 (m, 2H), 3.91 (s, 3H), 3.25 (s, 3H), 2.03 (s, 3H). LC/MS (Method B): 433.1 (M+H)+ HPLC: Rt 5.94 min (Purity: 94.9%).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. customto afford a yellow liquid
  3. additionunder N2 was added dropwise the yellow liquid
  4. additionthe addition
  5. waittook 15 min
  6. stirringThe reaction mixture was stirred at RT for 12 hours
  7. temperatureThen the mixture was refluxed for 24 hours
  8. temperatureThe reaction mixture was cooled to RT
  9. concentrationconcentrated
  10. customaffording a beige solid which
  11. washwas washed with MeOH (40 mL)
  12. filtrationThe suspension was filtered

출처 및 근거

ORD 기록
ord-fbfbc5b8955445178ae2b4742beae371
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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