Diisopropylethylamine → {4-[4-(3,5-Bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester

HRID 1468452노트

반응식

HRID 1468452 반응식
[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1.[F:25][C:26]([F:42])([F:41])[C:27]1[CH:28]=[C:29]([S:37](Cl)(=[O:39])=[O:38])[CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1.C(N(C(C)C)CC)(C)C>C1COCC1>[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][S:37]([C:29]3[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=[C:27]([C:26]([F:25])([F:41])[F:42])[CH:28]=3)(=[O:39])=[O:38])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 5209453,5-Bis(trifluoromethyl)benzenesulphonyl chlorideHCID 86694944[4-(4-Amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

생성물 1

HCID 86695030{4-[4-(3,5-Bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester수율 21.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of [4-(4-amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (55 mg, 0.17 mmol) and 3,5-bis(trifluoromethyl)benzenesulfonyl chloride (54 mg, 0.17 mmol) in THF (3 mL) was added diisopropylethylamine (62 mg, 0.48 mmol) at 0° C. under nitrogen. After addition, the reaction mixture was warmed to room temperature and stirred for 3 hours. The solvent was removed under vacuum and the residue was diluted with water (10 mL). The mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (20 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent under vacuum gave the crude residue which was purified using an ISCO (12 g) column, eluting with 2-25% ethyl acetate in hexanes, to afford {4-[4-(3,5-bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (21.5 mg, 21%) as a light brown solid. 1H NMR (300 MHz, CDCl3) δ ppm 8.23 (s, 2 H), 8.09 (s, 1 H), 7.78 (dd, J=8.8, 5.7 Hz, 1 H), 7.73 (s, 1 H), 7.11-7.24 (m, 5 H), 7.04 (s, 1 H), 6.73 (d, J=10.9 Hz, 1 H), 3.87 (s, 2 H), 3.75 (s, 3 H), 2.07 (s, 3 H). HRMS calcd. for C28H19F7NO4S [(M−H)−] 598.0928, obsd. 598.0925.

후처리

  1. additionAfter addition
  2. customThe solvent was removed under vacuum
  3. additionthe residue was diluted with water (10 mL)
  4. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  5. washThe combined organic extracts were washed with brine solution (20 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationFiltration of the drying agent and concentration of the solvent under vacuum
  8. customgave the crude residue which
  9. customwas purified
  10. washeluting with 2-25% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-07226840cd20458f86e3c0c6408ef4e2
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000044B2

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