4-Morpholinopiperidine → Methyl 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245167노트

반응식

HRID 245167 반응식
Br[CH2:2][C:3]1[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([O:15][CH3:16])=[O:14])=[CH:10][C:9]([S:17]([CH2:20][CH3:21])(=[O:19])=[O:18])=[C:8]([O:22][CH3:23])[CH:7]=2.[NH:34]1[CH2:39][CH2:38][CH:37]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH2:36][CH2:35]1>C(#N)C>[CH2:20]([S:17]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:22][CH3:23])[N:5]=[C:4]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1)[C:3]([CH2:2][N:34]1[CH2:39][CH2:38][CH:37]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[CH2:36][CH2:35]1)=[C:12]2[C:13]([O:15][CH3:16])=[O:14])(=[O:18])=[O:19])[CH3:21]

참가 물질

4

반응물 2

HCID 7957244-MorpholinopiperidineHCID 67417229Methyl 3-(bromomethyl)-6-(ethylsulfonyl)-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

생성물 1

HCID 67417221Methyl 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate수율 87%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A suspension of methyl 3-(bromomethyl)-6-(ethylsulfonyl)-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.983 g, 3.63 mmol) and 4-(4-piperidinyl)morpholine (0.803 g, 4.72 mmol) in acetonitrile (30 mL) was stirred for 3 hours. The solvent was removed under reduced pressure. The residue was dissolved in DMSO and purified via reverse phase HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with methylene chloride (3 times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to afford methyl 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.0 g, 87% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.98 (s, 1H), 7.90 (t, J=7.91 Hz, 2H), 7.75-7.84 (m, 2H), 4.10 (s, 3H), 4.01 (s, 3H), 3.61 (s, 2H), 3.50-3.58 (m, 6H), 2.63 (d, J=11.04 Hz, 2H), 2.38 (br. s., 4H), 1.93-2.08 (m, 1H), 1.81 (t, J=10.92 Hz, 2H), 1.61 (d, J=11.54 Hz, 2H), 1.22-1.30 (m, 2H), 1.15 (t, J=7.40 Hz, 3H); MS (m/z) 636.2 (M+H+).

후처리

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in DMSO
  3. custompurified via reverse phase HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA)
  4. additionThe fractions containing the product
  5. extractionextracted with methylene chloride (3 times)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-fadc3dd8f9b14529903987abb55faea6
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658636B2

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