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

HRID 245167ノート

反応式

HRID 245167 の反応式
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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-fadc3dd8f9b14529903987abb55faea6
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

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